Allostery in the Hsp70 chaperone proteins

Topics in Current Chemistry

Volumn 328, Issue , 2013, Pages 99-153

  Zuiderweg, Erik R P ^a   Bertelsen, Eric B ^a   Rousaki, Aikaterini ^b,c   Mayer, Matthias P ^d   Gestwicki, Jason E ^a   Ahmad, Atta ^a,d  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

^c GOETHE UNIVERSITY   (Germany)

^d UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

DnaJ; DnaK; Dynamics; Interactions; Structure

Indexed keywords

ADENOSINE TRIPHOSPHATE; HEAT SHOCK PROTEIN 70;

ALLOSTERISM; CHEMICAL STRUCTURE; CHEMISTRY; HYDROLYSIS; METABOLISM; REVIEW; X RAY CRYSTALLOGRAPHY;

ADENOSINE TRIPHOSPHATE; ALLOSTERIC REGULATION; CRYSTALLOGRAPHY, X-RAY; HSP70 HEAT-SHOCK PROTEINS; HYDROLYSIS; MODELS, MOLECULAR;

EID: 84874473589     PISSN: 03401022     EISSN: None     Source Type: Book Series    
DOI: 10.1007/128-2012-323     Document Type: Article

References (213)

1. Hightower LE (1991) Heat-shock, stress proteins, chaperones, and proteotoxicity. Cell 66:191-197
2. Marques C, Guo W, Pereira P, Taylor A, Patterson C, Evans PC, Shang F (2006) The triage of damaged proteins: degradation by the ubiquitin-proteasome pathway or repair by molecular chaperones. FASEB J 20:741-743
3. Bukau B, Weissman J, Horwich A (2006) Molecular chaperones and protein quality control. Cell 125:443-451
4. Sfatos CD, Gutin AM, Abkevich VI, Shakhnovich EI (1996) Simulations of chaperoneassisted folding. Biochemistry 35:334-339
5. Gupta RS (1998) Protein phylogenies and signature sequences: a reappraisal of evolutionary relationships among archaebacteria, eubacteria, and eukaryotes. Microbiol Mol Biol Rev 62:1435-1491
6. Zylicz M, Wawrzynow A (2001) Insights into the function of Hsp70 chaperones. IUBMB Life 51:283-287
7. Qian S-B, McDonough H, Boellmann F, Cyr DM, Patterson C (2006) CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70. Nature 440:551-555
8. Majeski AE, Dice JF (2004) Mechanisms of chaperone-mediated autophagy. Int J Biochem Cell Biol 36:2435-2444
9. Craig EA, Huang P, Aron R, Andrew A (2006) The diverse roles of J-proteins, the obligate Hsp70 co-chaperone. Rev Physiol Biochem Pharmacol 156:1-21
10. Tzankov S, Wong MJ, Shi K, Nassif C, Young JC (2008) Functional divergence between co-chaperones of Hsc70. J Biol Chem 283:27100-27109
11. Chappell TG, Konforti BB, Schmid SL, Rothman JE (1987) The ATPase core of a clathrin uncoating protein. J Biol Chem 262:746-751
12. Brinker A, Scheufler C, Von Der Mulbe F, Fleckenstein B, Herrmann C, Jung G, Moarefi I, Hartl FU (2002) Ligand discrimination by TPR domains. Relevance and selectivity of EEVDrecognition in Hsp70 x Hop x Hsp90 complexes. J Biol Chem 277:19265-19275
13. Wells AD, Rai SK, Salvato MS, Band H, Malkovsky M (1997) Restoration of MHC class I surface expression and endogenous antigen presentation by a molecular chaperone. Scand J Immunol 45:605-612
14. Shin BK, Wang H, Yim AM, Le Naour F, Brichory F, Jang JH, Zhao R, Puravs E, Tra J, Michael CW, Misek DE, Hanash SM (2003) Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. J Biol Chem 278:7607-7616
15. Nylandsted J, Brand K, JaattelaM(2000) Heat shock protein 70 is required for the survival of cancer cells. Ann N Y Acad Sci 926:122-125
16. Kaul Z, Yaguchi T, Kaul SC, Hirano T, Wadhwa R, Taira K (2003) Mortalin imaging in normal and cancer cells with quantum dot immuno-conjugates. Cell Res 13:503-507
17. Kaul SC, Yaguchi T, Taira K, Reddel RR, Wadhwa R (2003) Overexpressed mortalin (mot-2)/mthsp70/GRP75 and hTERT cooperate to extend the in vitro lifespan of human fibroblasts. Exp Cell Res 286:96-101
18. Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86-103
19. Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G (2006) Heat shock proteins 27 and 70: anti-apoptotic proteins with tumorigenic properties. Cell Cycle 5:2592-2601
20. Soti C, Csermely P (2002) Chaperones and aging: role in neurodegeneration and in other civilizational diseases. Neurochem Int 41:383-389
21. Soti C, Csermely P (2002) Chaperones come of age. Cell Stress Chaperones 7:186-190
22. Abarzua F, Sakaguchi M, Tanimoto R, Sonegawa H, Li DW, Edamura K, Kobayashi T, Watanabe M, Kashiwakura Y, Kaku H, Saika T, Nakamura K, Nasu Y, Kumon H, Huh NH (2007) Heat shock proteins play a crucial role in tumor-specific apoptosis by REIC/Dkk-3. Int J Mol Med 20:37-43
23. Lanneau D, Brunet M, Frisan E, Solary E, Fontenay M, Garrido C (2008) Heat shock proteins: essential proteins for apoptosis regulation. J Cell Mol Med 12:743-761
24. Calderwood SK, Ciocca DR (2008) Heat shock proteins: stress proteins with Janus-like properties in cancer. Int J Hyperthermia 24:31-39
25. Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI, Cohen GM, Green DR (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2:469-475
26. Garrido C, Schmitt E, Cande C, Vahsen N, Parcellier A, Kroemer G (2003) Hsp27 and Hsp70: potentially oncogenic apoptosis inhibitors. Cell Cycle 2:579-584
27. Kaul SC, Duncan EL, Englezou A, Takano S, Reddel RR, Mitsui Y, Wadhwa R (1998) Malignant transformation of NIH3T3 cells by overexpression of mot-2 protein. Oncogene 17:907-911
28. Walker C, Bottger S, Low B (2006) Mortalin-based cytoplasmic sequestration of p53 in a nonmammalian cancer model. Am J Pathol 168:1526-1530
29. Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Rev 33:95-130
30. Flaherty KM, Deluca-Flaherty C, McKay DB (1990) 3-Dimensional structure of the ATPase fragment of a 70 k heat-shock cognate protein. Nature 346:623-628
31. Bork P, Sander C, Valencia A (1992) An ATPase domain common to prokaryotic cell-cycle proteins, sugar kinases, actin, and Hsp70 heat-shock proteins. Proc Natl Acad Sci USA 89:7290-7294
32. O'Brien MC, Flaherty KM, McKay DB (1996) Lysine 71 of the chaperone protein Hsc70 Is essential for ATP hydrolysis. J Biol Chem 271:15874-15878
33. Wilbanks SM, DeLuca-Flaherty C, McKay DB (1994) Structural basis of the 70-kilodalton heat shock cognate protein ATP hydrolytic activity. I. Kinetic analyses of active site mutants. J Biol Chem 269:12893-12898
34. O'Brien MC, McKay DB (1995) How potassium affects the activity of the molecular chaperone Hsc70.I. Potassium is required for optimal ATPase activity. J Biol Chem 270:2247-2250
35. Vogel M, Mayer MP, Bukau B (2006) Allosteric regulation of Hsp70 chaperones involves a conserved interdomain linker. J Biol Chem 281:38705-38711
36. Morshauser RC, Wang H, Flynn GC, Zuiderweg ER (1995) The peptide-binding domain of the chaperone protein Hsc70 has an unusual secondary structure topology. Biochemistry 34:6261-6266
37. Zhu XT, Zhao X, Burkholder WF, Gragerov A, Ogata CM, Gottesman ME, Hendrickson WA (1996) Structural analysis of substrate binding by the molecular chaperone DnaK. Science 272:1606-1614
38. Bertelsen EB, Chang L, Gestwicki JE, Zuiderweg ERP (2009) Solution conformation of wildtype E. coli Hsp70 (DnaK) chaperone complexed with ADP and substrate. Proc Natl Acad Sci USA 106:8471-8476
39. Smock RG, Blackburn ME, Gierasch LM (2011) Conserved, disordered C terminus of DnaK enhances cellular survival upon stress and DnaK in vitro chaperone activity. J Biol Chem 286:31821-31829
40. Pidoux AL, Armstrong J (1992) Analysis of the BIP gene and identification of an ER retention signal in S. Pombe. EMBO J 11:1583-1591
41. Bukau B, Horwich AL (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92:351-366
42. Han WJ, Christen P (2003) Mechanism of the targeting action of DnaJ in the DnaK molecular chaperone system. J Biol Chem 278:19038-19043
43. Moreno-del Alamo M, Sanchez-Gorostiaga A, Serrano AM, Prieto A, Cuellar J, Martin- Benito J, Valpuesta JM, Giraldo R (2010) Structural analysis of the interactions between Hsp70 chaperones and the yeast DNA replication protein Orc4p. J Mol Biol 403:24-39
44. Mayer MP, Bukau B (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62:670-684
45. Schroder H, Langer T,Hartl FU, Bukau B (1993) Dnak Dnaj andGrpe forma cellular chaperone machinery capable of repairing heat-induced protein damage. EMBO J 12:4137-4144
46. Ziemienowicz A, Skowyra D, Zeilstra-Ryalls J, Fayet O, Georgopoulos C, Zylicz M (1993) Both the Escherichia coli chaperone systems, GroEL/GroES and DnaK/DnaJ/GrpE, can reactivate heat-treated RNA polymerase. Different mechanisms for the same activity. J Biol Chem 268:25425-25431
47. Diamant S, Ben-Zvi AP, Bukau B, Goloubinoff P (2000) Size-dependent disaggregation of stable protein aggregates by the DnaK chaperone machinery. J Biol Chem 275:21107-21113
48. Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852-1858
49. Yam AY, Xia Y, Lin HTJ, Burlingame A, Gerstein M, Frydman J (2008) Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies. Nat Struct Mol Biol 15:1255-1262
50. De los Rios P, Ben-Zvi A, Slutsky O, Azem A, Goloubinoff P (2006) Hsp70 chaperones accelerate protein translocation and the unfolding of stable protein aggregates by entropic pulling. Proc Natl Acad Sci USA 103:6166-6171
51. Sharma SK, De Los Rios P, Christen P, Lustig A, Goloubinoff P (2010) The kinetic parameters and energy cost of the Hsp70 chaperone as a polypeptide unfoldase. Nat Chem Biol 6:914-920
52. Goloubinoff P, De Los Rios P (2007) The mechanism of Hsp70 chaperones: (entropic) pulling the models together. Trends Biochem Sci 32:372-380
53. Szabo A, Langer T, Schroder H, Flanagan J, Bukau B, Hartl FU (1994) The ATP hydrolysisdependent reaction cycle of the Escherichia coli Hsp70 system DnaK, DnaJ, and GrpE. Proc Natl Acad Sci USA 91:10345-10349
54. Mayer MP, Rudiger S, Bukau B (2000) Molecular basis for interactions of the DnaK chaperone with substrates. Biol Chem 381:877-885
55. Schmid D, Baici A, Gehring H, Christen P (1994) Kinetics of molecular chaperone action. Science 263:971-973
56. McCarty JS, Buchberger A, Reinstein J, Bukau B (1995) The role of ATP in the functional cycle of the DnaK chaperone system. J Mol Biol 249:126-137
57. Kim DH, Lee YJ, Corry PM (1992) Constitutive Hsp70-oligomerization and its dependence on ATP binding. J Cell Physiol 153:353-361
58. Chang L, Bertelsen EB, Wisen S, Larsen EM, Zuiderweg ERP, Gestwicki JE (2008) Highthroughput screen for small molecules that modulate the ATPase activity of the molecular chaperone DnaK. Anal Biochem 372:167-176
59. Jayakumar J, Smolenski RT, Gray CC, Goodwin AT, Kalsi K, Amrani M, Yacoub MH (1998) Influence of heat stress on myocardial metabolism and functional recovery after cardioplegic arrest: a P-31 NMR study. Eur J Cardiothorac Surg 13:467-474
60. Theyssen H, Schuster HP, Packschies L, Bukau B, Reinstein J (1996) The second step of ATP binding to DnaK induces peptide release. J Mol Biol 263:657-670
61. Buchberger A, Theyssen H, Schroder H, McCarty JS, Virgallita G, Milkereit P, Reinstein J, Bukau B (1995) Nucleotide-induced conformational changes in the ATPase and substrate binding domains of the DnaK chaperone provide evidence for interdomain communication. J Biol Chem 270:16903-16910
62. Montgomery DL, Morimoto RI, Gierasch LM (1999) Mutations in the substrate binding domain of the Escherichia coli 70 kDa molecular chaperone, DnaK, which alter substrate affinity or interdomain coupling. J Mol Biol 286:915-932
63. Rist W, Graf C, Bukau B, Mayer MP (2006) Amide hydrogen exchange reveals conformational changes in hsp70 chaperones important for allosteric regulation. J Biol Chem 281:16493-16501
64. Revington M, Zhang Y, Yip GN, Kurochkin AV, Zuiderweg ER (2005) NMR investigations of allosteric processes in a two-domain Thermus thermophilus Hsp70 molecular chaperone. J Mol Biol 349:163-183
65. Swain JF, Dinler G, Sivendran R, Montgomery DL, Stotz M, Gierasch LM (2007) Hsp70 chaperone ligands control domain association via an allosteric mechanism mediated by the interdomain linker. Mol Cell 26:27-39
66. Bukau B, Walker GC (1989) Cellular defects caused by deletion of the Escherichia coli dnaK gene indicate roles for heat shock protein in normal metabolism. J Bacteriol 171:2337-2346
67. Georgopoulos CP (1977) New bacterial gene (Gropc) which affects lambda-DNA replication. Mol Gen Genet 151:35-39
68. Schlecht R, Erbse AH, Bukau B, Mayer MP (2011) Mechanics of Hsp70 chaperones enables differential interaction with client proteins. Nat Struct Mol Biol 18:345-351
69. Chang L, Thompson AD, Ung P, Carlson HA, Gestwicki JE (2010) Mutagenesis reveals the complex relationships between ATPase rate and the chaperone activities of Escherichia coli heat shock protein 70 (Hsp70/DnaK). J Biol Chem 285:21282-21291
70. Flaherty KM, Wilbanks SM, DeLuca-Flaherty C, McKay DB (1994) Structural basis of the 70-kilodalton heat shock cognate protein ATP hydrolytic activity. II. Structure of the active site with ADP or ATP bound to wild type and mutant ATPase fragment. J Biol Chem 269:12899-12907
71. Harrison CJ, Hayer-Hartl M, Di Liberto M, Hartl F, Kuriyan J (1997) Crystal structure of the nucleotide exchange factor GrpE bound to the ATPase domain of the molecular chaperone DnaK. Science 276:431-435
72. Osipiuk J, Walsh MA, Freeman BC, Morimoto RI, Joachimiak A (1999) Structure of a new crystal form of human Hsp70 ATPase domain. Acta Crystallogr D Biol Crystallogr 55:1105-1107
73. Morshauser RC, Hu W, Wang H, Pang Y, Flynn GC, Zuiderweg ER (1999) High-resolution solution structure of the 18 kDa substrate-binding domain of the mammalian chaperone protein Hsc70. J Mol Biol 289:1387-1403
74. Pellecchia M, Montgomery DL, Stevens SY, Vander Kooi CW, Feng HP, Gierasch LM, Zuiderweg ER (2000) Structural insights into substrate binding by the molecular chaperone DnaK. Nat Struct Biol 7:298-303
75. Bertelsen EB, Zhou H, Lowry DF, Flynn GC, Dahlquist FW (1999) Topology and dynamics of the 10 kDa C-terminal domain of DnaK in solution. Protein Sci 8:343-354
76. Jiang J, Prasad K, Lafer EM, Sousa R (2005) Structural basis of interdomain communication in the Hsc70 chaperone. Mol Cell 20:513-524
77. Chang YW, Sun YJ, Wang C, Hsiao CD (2008) Crystal structures of the 70-kDa heat shock proteins in domain disjoining conformation. J Biol Chem 283:15502-15511
78. Wang H, Pang Y, Kurochkin AV, Hu W, Flynn GC, Zuiderweg ERP (1998) The solution structure of the 21 kDa chaperone protein DnaK substrate binding domain: a preview of chaperone - protein interaction. Biochemistry 37:7929-7940
79. Swain JF, Schulz EG, Gierasch LM (2006) Direct comparison of a stable isolated Hsp70 substrate-binding domain in the empty and substrate-bound states. J Biol Chem281:1605-1611
80. Liu Q, Hendrickson WA (2007) Insights into hsp70 chaperone activity from a crystal structure of the yeast Hsp110 Sse1. Cell 131:106-120
81. Zhang Y, Zuiderweg ER (2004) The 70-kDa heat shock protein chaperone nucleotidebinding domain in solution unveiled as a molecular machine that can reorient its functional subdomains. Proc Natl Acad Sci USA 101:10272-10277
82. Bhattacharya A, Kurochkin AV, Yip GN, Zhang Y, Bertelsen EB, Zuiderweg ER (2009) Allostery in Hsp70 chaperones is transduced by subdomain rotations. J Mol Biol 388:475-490
83. Zhuravleva A, Gierasch LM (2011) Allosteric signal transmission in the nucleotide-binding domain of 70-kDa heat shock protein (Hsp70) molecular chaperones. Proc Natl Acad Sci USA 108:6987-6992
84. Sousa MC, McKay DB (1998) The hydroxyl of threonine 13 of the bovine 70-kDa heat shock cognate protein is essential for transducing the ATP-induced conformational change. Biochemistry 37:15392-15399
85. O'Brien MC, McKay DB (1993) Threonine 204 of the chaperone protein Hsc70 influences the structure of the active site, but is not essential for ATP hydrolysis. J Biol Chem 268:24323-24329
86. Gassler CS, Buchberger A, Laufen T, Mayer MP, Schroder H, Valencia A, Bukau B (1998) Mutations in the DnaK chaperone affecting interaction with the DnaJ cochaperone. Proc Natl Acad Sci USA 95:15229-15234
87. Barthel TK, Zhang J, Walker GC (2001) ATPase-defective derivatives of Escherichia coli DnaK that behave differently with respect to ATP-induced conformational change and peptide release. J Bacteriol 183:5482-5490
88. Rudiger S, Mayer MP, Schneider-Mergener J, Bukau B (2000) Modulation of substrate specificity of the DnaK chaperone by alteration of a hydrophobic arch. J Mol Biol 304:245-251
89. Vogel M, Bukau B, Mayer MP (2006) Allosteric regulation of Hsp70 chaperones by a proline switch. Mol Cell 21:359-367
90. Han W, Christen P (2001) Mutations in the interdomain linker region of DnaK abolish the chaperone action of the DnaK/DnaJ/GrpE system. FEBS Lett 497:55-58
91. Burkholder WF, Zhao X, Zhu X, Hendrickson WA, Gragerov A, Gottesman ME (1996) Mutations in the C-terminal fragment of DnaK affecting peptide binding. Proc Natl Acad Sci USA 93:10632-10637
92. Voisine C, Craig EA, Zufall N, von Ahsen O, Pfanner N, Voos W (1999) The protein import motor of mitochondria: unfolding and trapping of preproteins are distinct and separable functions of matrix Hsp70. Cell 97:565-574
93. Smock RG, Rivoire O, Russ WP, Swain JF, Leibler S, Ranganathan R, Gierasch LM (2010) An interdomain sector mediating allostery in Hsp70 molecular chaperones. Mol Syst Biol 6:414
94. Shi L, Kataoka M, Fink AL (1996) Conformational characterization of DnaK and its complexes by small-angle X-ray scattering. Biochemistry 35:3297-3308
95. Wilbanks SM, Chen L, Tsuruta H, Hodgson KO, McKay DB (1995) Solution small-angle X-ray scattering study of the molecular chaperone Hsc70 and its subfragments. Biochemistry 34:12095-12106
96. Mapa K, Sikor M, Kudryavtsev V, Waegemann K, Kalinin S, Seidel CAM, Neupert W, Lamb DC, Mokranjac D (2010) The conformational dynamics of the mitochondrial Hsp70 chaperone. Mol Cell 38:89-100
97. Buczynski G, Slepenkov SV, Sehorn MG, Witt SN (2001) Characterization of a lidless form of the molecular chaperone DnaK: deletion of the lid increases peptide on- and off-rate constants. J Biol Chem 276:27231-27236
98. Slepenkov SV, Witt SN (2002) Kinetic analysis of interdomain coupling in a lidless variant of the molecular chaperone DnaK: DnaK's lid inhibits transition to the low affinity state. Biochemistry 41:12224-12235
99. Chesnokova LS, Slepenkov SV, Protasevich II, Sehorn MG, Brouillette CG, Witt SN (2003) Deletion of DnaK's lid strengthens binding to the nucleotide exchange factor, GrpE: a kinetic and thermodynamic analysis. Biochemistry 42:9028-9040
100. Slepenkov SV, Patchen B, Peterson KM, Witt SN (2003) Importance of the D and E helices of the molecular chaperone DnaK for ATP binding and substrate release. Biochemistry 42:5867-5876
101. Slepenkov SV, Witt SN (1998) Kinetics of the reactions of the Escherichia coli molecular chaperone DnaK with ATP: evidence that a three-step reaction precedes ATP hydrolysis. Biochemistry 37:1015-1024
102. Slepenkov SV, Witt SN (1998) Peptide-induced conformational changes in the molecular chaperone DnaK. Biochemistry 37:16749-16756
103. Slepenkov SV, Witt SN (2002) The unfolding story of the Escherichia coli Hsp70 DnaK: is DnaK a holdase or an unfoldase? Mol Microbiol 45:1197-1206
104. Slepenkov SV, Witt SN (2003) Detection of a concerted conformational change in the ATPase domain of DnaK triggered by peptide binding. FEBS Lett 539:100-104
105. Buchberger A, Valencia A, McMacken R, Sander C, Bukau B (1994) The chaperone function of DnaK requires the coupling of ATPase activity with substrate binding through residue E171. Embo J 13:1687-1695
106. Laufen T, Mayer MP, Beisel C, Klostermeier D, Mogk A, Reinstein J, Bukau B (1999) Mechanism of regulation of hsp70 chaperones by DnaJ cochaperones. Proc Natl Acad Sci USA 96:5452-5457
107. Jiang J, Maes EG, Taylor AB, Wang L, Hinck AP, Lafer EM, Sousa R (2007) Structural basis of J cochaperone binding and regulation of Hsp70. Mol Cell 28:422-433
108. Revington M, Holder TM, Zuiderweg ER (2004) NMR study of nucleotide-induced changes in the nucleotide binding domain of Thermus thermophilus Hsp70 chaperone DnaK: implications for the allosteric mechanism. J Biol Chem 279:33958-33967
109. FischerMW, Losonczi JA,Weaver JL, Prestegard JH (1999) Domain orientation and dynamics in multidomain proteins from residual dipolar couplings. Biochemistry 38:9013-9022
110. Sondermann H, Scheufler C, Schneider C, Hohfeld J, Hartl FU, Moarefi I (2001) Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors. Science 291:1553-1557
111. Shomura Y, Dragovic Z, Chang HC, Tzvetkov N, Young JC, Brodsky JL, Guerriero V, Hartl FU, Bracher A (2005) Regulation of Hsp70 function by HspBP1: structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange. Mol Cell 17:367-379
112. Dragovic Z, Broadley SA, Shomura Y, Bracher A, Hartl FU (2006) Molecular chaperones of the Hsp110 family act as nucleotide exchange factors of Hsp70s. EMBO J 25:2519-2528
113. Arakawa A, Handa N, Ohsawa N, Shida M, Kigawa T, Hayashi F, Shirouzu M, Yokoyama S (2010) The C-terminal BAG domain of BAG5 induces conformational changes of the Hsp70 nucleotide-binding domain for ADP-ATP exchange. Structure 18:309-319
114. Stevens SY, Cai S, Pellecchia M, Zuiderweg ER (2003) The solution structure of the bacterial HSP70 chaperone protein domain DnaK(393-507) in complex with the peptide NRLLLTG. Protein Sci 12:2588-2596
115. Fernandez-Saiz V, Moro F, Arizmendi JM, Acebron SP, Muga A (2006) Ionic contacts at DnaK substrate binding domain involved in the allosteric regulation of lid dynamics. J Biol Chem 281:7479-7488
116. Banecki B, Zylicz M (1996) Real time kinetics of the DnaK/DnaJ/GrpE molecular chaperone machine action. J Biol Chem 271:6137-6143
117. Moro F, Fernandez V, Muga A (2003) Interdomain interaction through helices A and B of DnaK peptide binding domain. FEBS Lett 533:119-123
118. Mayer MP (2010) Gymnastics of molecular chaperones. Mol Cell 39:321-331
119. Zhang Q, Sun X, Watt ED, Al-Hashimi HM (2006) Resolving the motional modes that code for RNA adaptation. Science 311:653-656
120. Cooper A, Dryden DTF (1984) Allostery without conformational change - a plausible model. Eur Biophys J Biophys Lett 11:103-109
121. Lechtenberg BC, Johnson DJD, Freund SMV, Huntington JA (2010) NMR resonance assignments of thrombin reveal the conformational and dynamic effects of ligation. Proc Natl Acad Sci USA 107:14087-14092
122. Itoh K, Sasai M (2010) Entropic mechanism of large fluctuation in allosteric transition. Proc Natl Acad Sci USA 107:7775-7780
123. Tzeng SR, Kalodimos CG (2009) Dynamic activation of an allosteric regulatory protein. Nature 462:368-U139
124. Kern D, Zuiderweg ER (2003) The role of dynamics in allosteric regulation. Curr Opin Struct Biol 13:748-757
125. Stevens SY, Sanker S, Kent C, Zuiderweg ERP (2001) Delineation of the allosteric mechanism of a cytidylyltransferase exhibiting negative cooperativity. Nat Struct Biol 8:947-952
126. Maler L, Blankenship J, Rance M, Chazin WJ (2000) Site-site communication in the EF-hand Ca2+-binding protein calbindin D9k. Nat Struct Biol 7:245-250
127. Han WJ, Christen P (2004) cis-Effect of DnaJ on DnaK in ternary complexes with chimeric DnaK/DnaJ-binding peptides. FEBS Lett 563:146-150
128. Farr CD, Galiano FJ, Witt SN (1995) Large activation energy barriers to chaperone-peptide complex formation and dissociation. Biochemistry 34:15574-15582
129. Farr CD, Witt SN (1997) Kinetic evidence for peptide-induced oligomerization of the molecular chaperone DnaK at heat shock temperatures. Biochemistry 36:10793-10800
130. Farr CD, Slepenkov SV, Witt SN (1998) Visualization of a slow, ATP-induced structural transition in the bacterial molecular chaperone DnaK. J Biol Chem 273:9744-9748
131. Farr CD, Witt SN (1999) ATP lowers the activation enthalpy barriers to DnaK-peptide complex formation and dissociation. Cell Stress Chaperones 4:77-85
132. Varley P, Gronenborn AM, Christensen H, Wingfield PT, Pain RH, Clore GM (1993) Kinetics of folding of the all-beta sheet protein interleukin-1 beta. Science 260:1110-1113
133. Pierpaoli EV, Sandmeier E, Baici A, Schonfeld HJ, Gisler S, Christen P (1997) The power stroke of the DnaK/DnaJ/GrpE molecular chaperone system. J Mol Biol 269:757-768
134. Han WJ, Christen P (2003) Interdomain communication in the molecular chaperone DnaK. Biochem J 369:627-634
135. Siegenthaler RK, Christen P (2006) Tuning of DnaK chaperone action by nonnative protein sensor DnaJ and thermosensor GrpE. J Biol Chem 281:34448-34456
136. Goloubinoff P, Mogk A, Zvi AP, Tomoyasu T, Bukau B (1999) Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network. Proc Natl Acad Sci USA 96:13732-13737
137. Packschies L, Theyssen H, Buchberger A, Bukau B, Goody RS, Reinstein J (1997) GrpE accelerates nucleotide exchange of the molecular chaperone DnaK with an associative displacement mechanism. Biochemistry 36:3417-3422
138. Xu Z, Page RC, Gomes MM, Kohli E, Nix JC, Herr AB, Patterson C, Misra S (2008) Structural basis of nucleotide exchange and client binding by the Hsp70 cochaperone Bag2. Nat Struct Mol Biol 15:1309-1317
139. Schuermann JP, Jiang JW, Cuellar J, Llorca O, Wang LP, Gimenez LE, Jin SP, Taylor AB, Demeler B, Morano KA, Hart PJ, Valpuesta JM, Lafer EM, Sousa R (2008) Structure of the Hsp110: Hsc70 nucleotide exchange machine. Mol Cell 31:232-243
140. Kabani M, McLellan C, Raynes DA, Guerriero V, Brodsky JL (2002) HspBP1, a homologue of the yeast Fes1 and Sls1 proteins, is an Hsc70 nucleotide exchange factor. FEBS Lett 531:339-342
141. Grimshaw JPA, Jelesarov I, Siegenthaler RK, Christen P (2003) Thermosensor action of GrpE - the DnaK chaperone system at heat shock temperatures. J Biol Chem 278:19048-19053
142. Brehmer D, Gassler C, Rist W, Mayer MP, Bukau B (2004) Influence of GrpE on DnaKsubstrate interactions. J Biol Chem 279:27957-27964
143. Rudiger S, Schneider-Mergener J, Bukau B (2001) Its substrate specificity characterizes the DnaJ co-chaperone as a scanning factor for the DnaK chaperone. EMBO J 20:1042-1050
144. Rudiger S, Germeroth L, Schneider-Mergener J, Bukau B (1997) Substrate specificity of the DnaK chaperone determined by screening cellulose-bound peptide libraries. EMBO J 16:1501-1507
145. Feifel B, Schonfeld HJ, Christen P (1998) D-peptide ligands for the co-chaperone DnaJ. J Biol Chem 273:11999-12002
146. Suzuki H, Noguchi S, Arakawa H, Tokida T, Hashimoto M, Satow Y (2010) Peptide-binding sites as revealed by the crystal structures of the human Hsp40 Hdj1 C-terminal domain in complex with the octapeptide from human Hsp70. Biochemistry 49:8577-8584
147. Li JZ, Oian XG, Sha B (2003) The crystal structure of the yeast Hsp40 Ydj1 complexed with its peptide substrate. Structure 11:1475-1483
148. Pellecchia M, Szyperski T, Wall D, Georgopoulos C, Wuthrich K (1996) NMR structure of the J-domain and the Gly/Phe-rich region of the Escherichia coli DnaJ chaperone. J Mol Biol 260:236-250
149. Genevaux P, Fau-Schwager F, Fau K,Georgopoulos C,KelleyW(2002) Scanning mutagenesis identifies amino acid residues essential for the in vivo activity of the Escherichia coli DnaJ (Hsp40) J-domain. Genetics 162:1045-1053
150. Wall D, Zylicz M, Georgopoulos C (1994) The NH2-terminal 108 amino acids of the Escherichia coli DnaJ protein stimulate the ATPase activity of DnaK and are sufficient for lambda replication. J Biol Chem 269:5446-5451
151. Greene MK, Maskos K, Landry SJ (1998) Role of the J-domain in the cooperation of Hsp40 with Hsp70. Proc Natl Acad Sci USA 95:6108-6113
152. Ahmad A, Bhattacharya A, McDonald RA, Cordes M, Ellington B, Bertelsen EB, Zuiderweg ER (2011) Heat shock protein 70 kDa chaperone/DnaJ cochaperone complex employs an unusual dynamic interface. Proc Natl Acad Sci USA 108:18966-18971
153. Wittung-Stafshede P, Guidry J, Horne BE, Landry SJ (2003) The J-domain of Hsp40 couples ATP hydrolysis to substrate capture in Hsp70. Biochemistry 42:4937-4944
154. Huang K, Flanagan JM, Prestegard JH (1999) The influence of C-terminal extension on the structure of the "J-domain" in E. coli DnaJ. Protein Sci 8:203-214
155. Cajo GC, Horne BE, Kelley WL, Schwager F, Georgopoulos C, Genevaux P (2006) The role of the DIF motif of the DnaJ (Hsp40) co-chaperone in the regulation of the DnaK (Hsp70) chaperone cycle. J Biol Chem 281:12436-12444
156. Suh WC, Burkholder WF, Lu CZ, Zhao X, Gottesman ME, Gross CA (1998) Interaction of the Hsp70 molecular chaperone, DnaK, with its cochaperone DnaJ. Proc Natl Acad Sci USA 95:15223-15228
157. Suh WC, Lu CZ, Gross CA (1999) Structural features required for the interaction of the Hsp70 molecular chaperone DnaK with its cochaperone DnaJ. J Biol Chem 274:30534-30539
158. Wall D, Zylicz M, Georgopoulos C (1995) The conserved G/F motif of the DnaJ chaperone is necessary for the activation of the substrate binding properties of the DnaK chaperone. J Biol Chem 270:2139-2144
159. Karzai AW, McMacken R (1996) A bipartite signaling mechanism involved in DnaJmediated activation of the Escherichia coli DnaK protein. J Biol Chem 271:11236-11246
160. Pierpaoli EV, Sandmeier E, Schonfeld HJ, Christen P (1998) Control of the DnaK chaperone cycle by substoichiometric concentrations of the co-chaperones DnaJ and GrpE. J Biol Chem 273:6643-6649
161. Horne BE, Li TF, Genevaux P, Georgopoulos C, Landry SJ (2010) The Hsp40 J-domain stimulates Hsp70 when tethered by the client to the ATPase domain. J Biol Chem 285:21679-21688
162. Yochem J, Uchida H, Sunshine M, Saito H, Georgopoulos CP, Feiss M (1978) Geneticanalysis of 2 genes, DnaJ and DnaK, necessary for Escherichia-coli and Bacteriophagelambda DNA-eeplication. Mol Gen Genet 164:9-14
163. Patury S, Miyata Y, Gestwicki JE (2009) Pharmacological targeting of the Hsp70 chaperone. Curr Top Med Chem 9:1337-1351
164. Nihei T, Sato N, Takahashi S, Ishikawa M, Sagae S, Kudo R, Kikuchi K, Inoue A (1993) Demonstration of selective protein complexes of p53 with 73 kDa heat shock cognate protein, but not with 72 kDa heat shock protein in human tumor cells. Cancer Lett 73:181-189
165. Fourie AM, Hupp TR, Lane DP, Sang BC, Barbosa MS, Sambrook JF, Gething MJ (1997) HSP70 binding sites in the tumor suppressor protein p53. J Biol Chem 272:19471-19479
166. Zylicz M, King FW, Wawrzynow A (2001) Hsp70 interactions with the p53 tumour suppressor protein. EMBO J 20:4634-4638
167. Wadhwa R, Yaguchi T, Hasan MK, Mitsui Y, Reddel RR, Kaul SC (2002) Hsp70 family member, mot-2/mthsp70/GRP75, binds to the cytoplasmic sequestration domain of the p53 protein. Exp Cell Res 274:246-253
168. Bienemann AS, Lee YB, Howarth J, Uney JB (2008) Hsp70 suppresses apoptosis in sympathetic neurones by preventing the activation of c-Jun. J Neurochem 104:271-278
169. Hui-Qing X, Jian-da Z, Xin-Min N, Yan-Zhong Z, Cheng-Qun L, Quan-Yong H, Yi X, Babu Pokharel P, Shao-Hua W, Dan X (2008) HSP70 inhibits burn serum-induced apoptosis of cardiomyocytes via mitochondrial and membrane death receptor pathways. J Burn Care Res 29:512-518
170. Guo F, Sigua C, Bali P, George P, Fiskus W, Scuto A, Annavarapu S, Mouttaki A, Sondarva G, Wei S, Wu J, Djeu J, Bhalla K (2005) Mechanistic role of heat shock protein 70 in Bcr-Abl-mediated resistance to apoptosis in human acute leukemia cells. Blood 105:1246-1255
171. Gyrd-Hansen M, Nylandsted J, Jaattela M (2004) Heat shock protein 70 promotes cancer cell viability by safeguarding lysosomal integrity. Cell Cycle 3:1484-1485
172. Didelot C, Lanneau D, Brunet M, Joly AL, De Thonel A, Chiosis G, Garrido C (2007) Anticancer therapeutic approaches based on intracellular and extracellular heat shock proteins. Curr Med Chem 14:2839-2847
173. Wadhwa R, Takano S, Robert M, Yoshida A, Nomura H, Reddel RR, Mitsui Y, Kaul SC (1998) Inactivation of tumor suppressor p53 by mot-2, a hsp70 family member. J Biol Chem 273:29586-29591
174. Lehman TA, Bennett WP,Metcalf RA,Welsh JA, Ecker J,Modali RV, Ullrich S, Romano JW, Appella E, Testa JR et al (1991) p53 mutations, ras mutations, and p53-heat shock 70 protein complexes in human lung carcinoma cell lines. Cancer Res 51:4090-4096
175. King FW, Wawrzynow A, Hohfeld J, Zylicz M(2001) Co-chaperones Bag-1, Hop and Hsp40 regulate Hsc70 and Hsp90 interactions with wild-type or mutant p53. EMBO J 20:6297-6305
176. Lane DP, Midgley C, Hupp T (1993) Tumour suppressor genes and molecular chaperones. Philos Trans R Soc Lond B Biol Sci 339:369-372, discussion 372-3
177. Vargas-Roig LM, Fanelli MA, Lopez LA, Gago FE, Tello O, Aznar JC, Ciocca DR (1997) Heat shock proteins and cell proliferation in human breast cancer biopsy samples. Cancer Detect Prev 21:441-451
178. Nylandsted J, Wick W, Hirt UA, Brand K, Rohde M, Leist M, Weller M, Jaattela M (2002) Eradication of glioblastoma, and breast and colon carcinoma xenografts by Hsp70 depletion. Cancer Res 62:7139-7142
179. Wadhwa R, Takano S, Taira K, Kaul SC (2004) Reduction in mortalin level by its antisense expression causes senescence-like growth arrest in human immortalized cells. J Gene Med 6:439-444
180. Modica-Napolitano JS, Koya K, Weisberg E, Brunelli BT, Li Y, Chen LB (1996) Selective damage to carcinoma mitochondria by the rhodacyanine MKT-077. Cancer Res 56:544-550
181. Rodina A, Vilenchik M, Moulick K, Aguirre J, Kim J, Chiang A, Litz J, Clement CC, Kang Y, She Y, Wu N, Felts S, Wipf P, Massague J, Jiang X, Brodsky JL, Krystal GW, Chiosis G (2007) Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer. Nat Chem Biol 3:498-507
182. Massey AJ, Wood M (2010) A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol 66:535-545
183. Ermakova SP, Kang BS, Choi BY, Choi HS, Schuster TF, Ma WY, Bode AM, Dong Z (2006) (-)-Epigallocatechin gallate overcomes resistance to etoposide-induced cell death by targeting the molecular chaperone glucose-regulated protein 78. Cancer Res 66:9260-9269
184. Wadhwa R, Sugihara T, Yoshida A, Nomura H, Reddel RR, Simpson R, Maruta H, Kaul SC (2000) Selective toxicity of MKT-077 to cancer cells is mediated by its binding to the hsp70 family protein mot-2 and reactivation of p53 function. Cancer Res 60:6818-6821
185. Wadhwa R, Takano S, Mitsui Y, Kaul SC (1999) NIH 3 T3 cells malignantly transformed by mot-2 show inactivation and cytoplasmic sequestration of the p53 protein. Cell Res 9:261-269
186. Britten CD, Rowinsky EK, Baker SD, Weiss GR, Smith L, Stephenson J, Rothenberg M, Smetzer L, Cramer J, Collins W, Von Hoff DD, Eckhardt SG (2000) A phase I and pharmacokinetic study of the mitochondrial-specific rhodacyanine dye analog MKT 077. Clin Cancer Res 6:42-49
187. Koo EH, Lansbury PT, Kelly JW (1999) Amyloid diseases: abnormal protein aggregation in neurodegeneration. Proc Natl Acad Sci USA 96:9989-9990
188. Caughey B, Lansbury PT (2003) Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu Rev Neurosci 26:267-298
189. Selkoe DJ (2003) Folding proteins in fatal ways. Nature 426:900-904
190. Avila J, Lucas JJ, Perez M, Hernandez F (2004) Role of tau protein in both physiological and pathological conditions. Physiol Rev 84:361-384
191. Bramblett GT, Goedert M, Jakes R, Merrick SE, Trojanowski JQ, Lee VMY (1993) Abnormal tau-phosphorylation at ser(396) in Alzheimers disease recapitulates development and contributes to reduced microtubule binding. Neuron 10:1089-1099
192. Geschwind DH (2003) Tau phosphorylation, tangles, and neurodegeneration: the chicken or the egg? Neuron 40:457-460
193. Boutajangout A, Quartermain D, Sigurdsson EM(2010) Immunotherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model. J Neurosci 30:16559-16566
194. Dou F, Netzer WJ, Tanemura K, Li F, Hartl FU, Takashima A, Gouras GK, Greengard P, Xu H (2003) Chaperones increase association of tau protein with microtubules. Proc Natl Acad Sci USA 100:721-726
195. Jinwal UK, Miyata Y, Koren J 3rd, Jones JR, Trotter JH, Chang L, O'Leary J, Morgan D, Lee DC, Shults CL, Rousaki A, Weeber EJ, Zuiderweg ER, Gestwicki JE, Dickey CA (2009) Chemical manipulation of hsp70 ATPase activity regulates tau stability. J Neurosci 29:12079-12088
196. Powers MV, Jones K, Barillari C, Westwood I, van Montfort RLM, Workman P (2010) Targeting HSP70: the second potentially druggable heat shock protein and molecular chaperone? Cell Cycle 9:1542-1550
197. Williamson DS, Borgognoni J, Clay A, Daniels Z, Dokurno P, Drysdale MJ, Foloppe N, Francis GL, Graham CJ, Howes R, Macias AT, Murray JB, Parsons R, Shaw T, Surgenor AE, Terry L, Wang YK, Wood M, Massey AJ (2009) Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design. J Med Chem 52:1510-1513
198. Kragol G, Lovas S, Varadi G, Condie BA, Hoffmann R, Otvos L (2001) The antibacterial peptide pyrrhocoricin inhibits the ATPase actions of DnaK and prevents chaperone-assisted protein folding. Biochemistry 40:3016-3026
199. Hohfeld J, Minami Y, Hartl F-U (1995) Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle. Cell 83:589-598
200. Johnson BD, Schumacher RJ, Ross ED, Toft DO (1998) Hop modulates Hsp70/Hsp90 interactions in protein folding. J Biol Chem 273:3679-3686
201. Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Hohfeld J, Patterson C (2001) The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol 3:93-96
202. Burri L, Vascotto K, Fredersdorf S, Tiedt R, Hall MN, Lithgow T (2004) Zim17, a novel zinc finger protein essential for protein import into mitochondria. J Biol Chem 279:50243-50249
203. Wisen S, Bertelsen EB, Thompson AD, Patury S, Ung P, Chang L, Evans CG, Walter GM, Wipf P, Carlson HA, Brodsky JL, Zuiderweg ERP, Gestwicki JE (2010) Binding of a small molecule at a protein-protein interface regulates the chaperone activity of Hsp70-Hsp40. ACS Chem Biol 5:611-622
204. Chang L, Miyata Y, Ung PM, Bertelsen EB, McQuade TJ, Carlson HA, Zuiderweg ER, Gestwicki JE (2011) Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism. Chem Biol 18:210-221
205. Rousaki A, Miyata Y, Jinwal UK, Dickey CA, Gestwicki JE, Zuiderweg ER (2011) Allosteric drugs: the interaction of antitumor compound MKT-077 with human Hsp70 chaperones. J Mol Biol 411:614-632
206. Tikoo A, Shakri R, Connolly L, Hirokawa Y, Shishido T, Bowers B, Ye LH, Kohama K, Simpson RJ, Maruta H (2000) Treatment of ras-induced cancers by the F-actin-bundling drug MKT-077. Cancer J 6:162-168
207. Koya K, Li Y, Wang H, Ukai T, Tatsuta N, Kawakami M, Shishido, Chen LB (1996) MKT- 077, a novel rhodacyanine dye in clinical trials, exhibits anticarcinoma activity in preclinical studies based on selective mitochondrial accumulation. Cancer Res 56:538-543
208. O'Leary JC, Li QY, Marinec P, Blair LJ, Congdon EE, Johnson AG, Jinwal UK, Koren J, Jones JR, Kraft C, Peters M, Abisambra JF, Duff KE, Weeber EJ, Gestwicki JE, Dickey CA (2010) Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Mol Neurodegener 5:45
209. Dickey CA, Koren J, Zhang YJ, Xu YF, Jinwal UK, Birnbaum MJ, Monks B, Sun M, Cheng AQ, Pattersonl C, Bailey RM, Dunmore J, Soresh S, Leon C, Morgan D, Petrucelli L (2008) Akt and CHIP coregulate tau degradation through coordinated interactions. Proc Natl Acad Sci USA 105:3622-3627
210. Arnone A, Perutz MF (1974) Structure of inositol hexaphosphate-human deoxyhemoglobin complex. Nature 249:34-36
211. Morris G, Goodsell D, Pique M, Lindstrom W, Huey R, Forli S, Hart W, Halliday S, Belew R, Olson A (2010) AutoDock Version 4.2
212. Case DA, Cheatham TE 3rd, Darden T, Gohlke H, Luo R, Merz KM Jr, Onufriev A, Simmerling C, Wang B, Woods RJ (2005) The Amber biomolecular simulation programs. J Comput Chem 26:1668-1688
213. Fogolari F, Brigo A, Molinari H (2003) Protocol for MM/PBSA molecular dynamics simulations of proteins. Biophys J 85:159-166