Structural and mechanistic principles of intramembrane proteolysis - Lessons from rhomboids

FEBS Journal

Volumn 280, Issue 7, 2013, Pages 1579-1603

  Strisovsky, Kvido ^a  

^a INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY   (Czech Republic)

Author keywords

secretase; crystal structure; enzymatic mechanism; intramembrane protease; presenilin; rhomboid; signal peptide peptidase; site 2 protease; substrate specificity

Indexed keywords

ARCHAEAL PREFLAGELLIN; BACTERIAL TYPE 4 PREPILIN PEPTIDASE; CYTOCHROME C PEROXIDASE; EPIDERMAL GROWTH FACTOR RECEPTOR; METALLOPROTEINASE; PRESENILIN; PROTEINASE; RHOMBOID; SIGNAL PEPTIDE PEPTIDASE LIKE PROTEASE; UNCLASSIFIED DRUG;

BINDING AFFINITY; BIOLOGICAL FUNCTIONS; CATALYSIS; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME DEGRADATION; ENZYME MECHANISM; ENZYME REGULATION; ENZYME SPECIFICITY; ENZYME STRUCTURE; ENZYME SUBSTRATE; ENZYME SUBSTRATE COMPLEX; EVOLUTION; GENETIC VARIABILITY; HYDROPHOBICITY; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN CONFORMATION; PROTEIN MOTIF; PROTEIN PROTEIN INTERACTION; REVIEW; SEQUENCE ANALYSIS;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; ASPARTIC ACID PROTEASES; BACTERIAL PROTEINS; CATALYTIC DOMAIN; DNA-BINDING PROTEINS; DROSOPHILA PROTEINS; ENDOPEPTIDASES; ESCHERICHIA COLI PROTEINS; EVOLUTION, MOLECULAR; MEMBRANE PROTEINS; METALLOENDOPEPTIDASES; MOLECULAR SEQUENCE DATA; PRESENILINS; PROTEIN CONFORMATION; PROTEOLYSIS; SERINE PROTEASES; SUBSTRATE SPECIFICITY;

PROKARYOTA;

EID: 84875871162     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/febs.12199     Document Type: Review

References (163)

1. Rawson RB, Zelenski NG, Nijhawan D, Ye J, Sakai J, Hasan MT, Chang TY, Brown MS, &, Goldstein JL, (1997) Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs. Mol Cell 1, 47-57.
2. Weihofen A, Binns K, Lemberg MK, Ashman K, &, Martoglio B, (2002) Identification of signal peptide peptidase, a presenilin-type aspartic protease. Science 296, 2215-2218.
3. Urban S, Lee JR, &, Freeman M, (2001) Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases. Cell 107, 173-182.
4. Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, &, Selkoe DJ, (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398, 513-517.
5. Brown MS, Ye J, Rawson RB, &, Goldstein JL, (2000) Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100, 391-398.
6. Sakai J, Duncan EA, Rawson RB, Hua X, Brown MS, &, Goldstein JL, (1996) Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment. Cell 85, 1037-1046.
7. Levitan D, &, Greenwald I, (1995) Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature 377, 351-354.
8. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, et al,. (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518-522.
9. Huppert SS, Le A, Schroeter EH, Mumm JS, Saxena MT, Milner LA, &, Kopan R, (2000) Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1. Nature 405, 966-970.
10. Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, et al,. (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375, 754-760.
11. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, et al,. (1996) Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat Med 2, 864-870.
12. De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, &, Van Leuven F, (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391, 387-390.
13. Zhang Z, Nadeau P, Song W, Donoviel D, Yuan M, Bernstein A, &, Yankner BA, (2000) Presenilins are required for gamma-secretase cleavage of beta-APP and transmembrane cleavage of Notch-1. Nat Cell Biol 2, 463-465.
14. Lee JR, Urban S, Garvey CF, &, Freeman M, (2001) Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila. Cell 107, 161-171.
15. Urban S, &, Freeman M, (2002) Intramembrane proteolysis controls diverse signalling pathways throughout evolution. Curr Opin Genet Dev 12, 512-518.
16. Shi G, Lee JR, Grimes DA, Racacho L, Ye D, Yang H, Ross OA, Farrer M, McQuibban GA, &, Bulman DE, (2011) Functional alteration of PARL contributes to mitochondrial dysregulation in Parkinson's disease. Hum Mol Genet 20, 1966-1974.
17. Whitworth AJ, Lee JR, Ho VM, Flick R, Chowdhury R, &, McQuibban GA, (2008) Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's disease factors Pink1 and Parkin. Dis Model Mech 1, 168-174. discussion 173.
18. Hatunic M, Stapleton M, Hand E, DeLong C, Crowley VE, &, Nolan JJ, (2009) The Leu262Val polymorphism of presenilin associated rhomboid like protein (PARL) is associated with earlier onset of type 2 diabetes and increased urinary microalbumin creatinine ratio in an Irish case-control population. Diabetes Res Clin Pract 83, 316-319.
19. Walder K, Kerr-Bayles L, Civitarese A, Jowett J, Curran J, Elliott K, Trevaskis J, Bishara N, Zimmet P, Mandarino L, et al,. (2005) The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes. Diabetologia 48, 459-468.
20. Blaydon DC, Etheridge SL, Risk JM, Hennies HC, Gay LJ, Carroll R, Plagnol V, McRonald FE, Stevens HP, Spurr NK, et al,. (2012) RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. Am J Hum Genet 90, 340-346.
21. Urban S, (2009) Making the cut: central roles of intramembrane proteolysis in pathogenic microorganisms. Nat Rev Microbiol 7, 411-423.
22. Beisner DR, Langerak P, Parker AE, Dahlberg C, Otero FJ, Sutton SE, Poirot L, Barnes W, Young MA, Niessen S, et al,. (2013) The intramembrane protease Spp l2a is required for B cell and DC development and survival via cleavage of the invariant chain. J Exp Med 210, 23-30.
23. Bergmann H, Yabas M, Short A, Miosge L, Barthel N, Teh CE, Roots CM, Bull KR, Jeelall Y, Horikawa K, et al,. (2013) B cell survival, surface BCR and BAFFR expression, CD74 metabolism, and CD8- dendritic cells require the intramembrane endopeptidase SPPL2A. J Exp Med 210, 31-40.
24. Schneppenheim J, Dressel R, Huttl S, Lullmann-Rauch R, Engelke M, Dittmann K, Wienands J, Eskelinen EL, Hermans-Borgmeyer I, Fluhrer R, et al,. (2013) The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain. J Exp Med 210, 41-58.
25. Rawlings ND, Barrett AJ, &, Bateman A, (2012) MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res 40, D343-D350.
26. Kinch LN, Ginalski K, &, Grishin NV, (2006) Site-2 protease regulated intramembrane proteolysis: sequence homologs suggest an ancient signaling cascade. Protein Sci 15, 84-93.
27. Koonin EV, Makarova KS, Rogozin IB, Davidovic L, Letellier MC, &, Pellegrini L, (2003) The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers. Genome Biol 4, R19.
28. Lemberg MK, &, Freeman M, (2007) Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases. Genome Res 17, 1634-1646.
29. Steiner H, Kostka M, Romig H, Basset G, Pesold B, Hardy J, Capell A, Meyn L, Grim ML, Baumeister R, et al,. (2000) Glycine 384 is required for presenilin-1 function and is conserved in bacterial polytopic aspartyl proteases. Nat Cell Biol 2, 848-851.
30. LaPointe CF, &, Taylor RK, (2000) The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases. J Biol Chem 275, 1502-1510.
31. Urban S, &, Wolfe MS, (2005) Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity. Proc Natl Acad Sci USA 102, 1883-1888.
32. Lemberg MK, Menendez J, Misik A, Garcia M, Koth CM, &, Freeman M, (2005) Mechanism of intramembrane proteolysis investigated with purified rhomboid proteases. EMBO J 24, 464-472.
33. Maegawa S, Ito K, &, Akiyama Y, (2005) Proteolytic action of GlpG, a rhomboid protease in the Escherichia coli cytoplasmic membrane. Biochemistry 44, 13543-13552.
34. Mayer U, &, Nusslein-Volhard C, (1988) A group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo. Genes Dev 2, 1496-1511.
35. Sturtevant MA, Roark M, &, Bier E, (1993) The Drosophila rhomboid gene mediates the localized formation of wing veins and interacts genetically with components of the EGF-R signaling pathway. Genes Dev 7, 961-973.
36. Bier E, Jan LY, &, Jan YN, (1990) rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster. Genes Dev 4, 190-203.
37. Bang AG, &, Kintner C, (2000) Rhomboid and Star facilitate presentation and processing of the Drosophila TGF-alpha homolog Spitz. Genes Dev 14, 177-186.
38. Wasserman JD, Urban S, &, Freeman M, (2000) A family of rhomboid-like genes: Drosophila rhomboid-1 and roughoid/rhomboid-3 cooperate to activate EGF receptor signaling. Genes Dev 14, 1651-1663.
39. Adrain C, &, Freeman M, (2012) New lives for old: evolution of pseudoenzyme function illustrated by iRhoms. Nat Rev Mol Cell Biol 13, 489-498.
40. Zettl M, Adrain C, Strisovsky K, Lastun V, &, Freeman M, (2011) Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling. Cell 145, 79-91.
41. Adrain C, Zettl M, Christova Y, Taylor N, &, Freeman M, (2012) Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. Science 335, 225-228.
42. Greenblatt EJ, Olzmann JA, &, Kopito RR, (2011) Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant alpha-1 antitrypsin from the endoplasmic reticulum. Nat Struct Mol Biol 18, 1147-1152.
43. Christianson JC, Olzmann JA, Shaler TA, Sowa ME, Bennett EJ, Richter CM, Tyler RE, Greenblatt EJ, Harper JW, &, Kopito RR, (2012) Defining human ERAD networks through an integrative mapping strategy. Nat Cell Biol 14, 93-105.
44. Freeman M, (2008) Rhomboid proteases and their biological functions. Annu Rev Genet 42, 191-210.
45. Urban S, &, Dickey SW, (2011) The rhomboid protease family: a decade of progress on function and mechanism. Genome Biol 12, 231.
46. Urban S, Lee JR, &, Freeman M, (2002) A family of Rhomboid intramembrane proteases activates all Drosophila membrane-tethered EGF ligands. EMBO J 21, 4277-4286.
47. Dutt A, Canevascini S, Froehli-Hoier E, &, Hajnal A, (2004) EGF signal propagation during C. elegans vulval development mediated by ROM-1 rhomboid. PLoS Biol 2, e334.
48. Fleig L, Bergbold N, Sahasrabudhe P, Geiger B, Kaltak L, &, Lemberg MK, (2012) Ubiquitin-dependent intramembrane rhomboid protease promotes ERAD of membrane proteins. Mol Cell 47, 558-569.
49. McQuibban GA, Saurya S, &, Freeman M, (2003) Mitochondrial membrane remodelling regulated by a conserved rhomboid protease. Nature 423, 537-541.
50. Herlan M, Vogel F, Bornhovd C, Neupert W, &, Reichert AS, (2003) Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA. J Biol Chem 278, 27781-27788.
51. McQuibban GA, Lee JR, Zheng L, Juusola M, &, Freeman M, (2006) Normal mitochondrial dynamics requires rhomboid-7 and affects Drosophila lifespan and neuronal function. Curr Biol 16, 982-989.
52. Cipolat S, Rudka T, Hartmann D, Costa V, Serneels L, Craessaerts K, Metzger K, Frezza C, Annaert W, D'Adamio L, et al,. (2006) Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell 126, 163-175.
53. Santos JM, Ferguson DJ, Blackman MJ, &, Soldati-Favre D, (2011) Intramembrane cleavage of AMA1 triggers Toxoplasma to switch from an invasive to a replicative mode. Science 331, 473-477.
54. Baker RP, Wijetilaka R, &, Urban S, (2006) Two Plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria. PLoS Pathog 2, e113.
55. Howell SA, Hackett F, Jongco AM, Withers-Martinez C, Kim K, Carruthers VB, &, Blackman MJ, (2005) Distinct mechanisms govern proteolytic shedding of a key invasion protein in apicomplexan pathogens. Mol Microbiol 57, 1342-1356.
56. Dowse TJ, Pascall JC, Brown KD, &, Soldati D, (2005) Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion. Int J Parasitol 35, 747-756.
57. Srinivasan P, Coppens I, &, Jacobs-Lorena M, (2009) Distinct roles of Plasmodium rhomboid 1 in parasite development and malaria pathogenesis. PLoS Pathog 5, e1000262.
58. Buguliskis JS, Brossier F, Shuman J, &, Sibley LD, (2010) Rhomboid 4 (ROM4) affects the processing of surface adhesins and facilitates host cell invasion by Toxoplasma gondii. PLoS Pathog 6, e1000858.
59. Brossier F, Jewett TJ, Sibley LD, &, Urban S, (2005) A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma. Proc Natl Acad Sci USA 102, 4146-4151.
60. Vera IM, Beatty WL, Sinnis P, &, Kim K, (2011) Plasmodium protease ROM1 is important for proper formation of the parasitophorous vacuole. PLoS Pathog 7, e1002197.
61. Brossier F, Starnes GL, Beatty WL, &, Sibley LD, (2008) Microneme rhomboid protease TgROM1 is required for efficient intracellular growth of Toxoplasma gondii. Eukaryot Cell 7, 664-674.
62. Palmer T, &, Berks BC, (2012) The twin-arginine translocation (Tat) protein export pathway. Nat Rev Microbiol 10, 483-496.
63. Stevenson LG, Strisovsky K, Clemmer KM, Bhatt S, Freeman M, &, Rather PN, (2007) Rhomboid protease AarA mediates quorum-sensing in Providencia stuartii by activating TatA of the twin-arginine translocase. Proc Natl Acad Sci USA 104, 1003-1008.
64. Rather PN, Parojcic MM, &, Paradise MR, (1997) An extracellular factor regulating expression of the chromosomal aminoglycoside 2'-N-acetyltransferase of Providencia stuartii. Antimicrob Agents Chemother 41, 1749-1754.
65. Rather PN, Ding X, Baca-DeLancey RR, &, Siddiqui S, (1999) Providencia stuartii genes activated by cell-to-cell signaling and identification of a gene required for production or activity of an extracellular factor. J Bacteriol 181, 7185-7191.
66. Higy M, Junne T, &, Spiess M, (2004) Topogenesis of membrane proteins at the endoplasmic reticulum. Biochemistry 43, 12716-12722.
67. Urban S, Schlieper D, &, Freeman M, (2002) Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic rhomboids. Curr Biol 12, 1507-1512.
68. Loughlin WA, Tyndall JD, Glenn MP, Hill TA, &, Fairlie DP, (2010) Update 1 of: Beta-strand mimetics. Chem Rev 110, PR32-PR69.
69. Tyndall JD, &, Fairlie DP, (1999) Conformational homogeneity in molecular recognition by proteolytic enzymes. J Mol Recognit 12, 363-370.
70. Madala PK, Tyndall JD, Nall T, &, Fairlie DP, (2010) Update 1 of: proteases universally recognize beta strands in their active sites. Chem Rev 110, PR1-31.
71. Schechter I, &, Berger A, (1967) On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun 27, 157-162.
72. Betzel C, Bellemann M, Pal GP, Bajorath J, Saenger W, &, Wilson KS, (1988) X-ray and model-building studies on the specificity of the active site of proteinase K. Proteins 4, 157-164.
73. Ye J, Dave UP, Grishin NV, Goldstein JL, &, Brown MS, (2000) Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by site-2 protease. Proc Natl Acad Sci USA 97, 5123-5128.
74. Lemberg MK, &, Martoglio B, (2002) Requirements for signal peptide peptidase-catalyzed intramembrane proteolysis. Mol Cell 10, 735-744.
75. Hessa T, Kim H, Bihlmaier K, Lundin C, Boekel J, Andersson H, Nilsson I, White SH, &, von Heijne G, (2005) Recognition of transmembrane helices by the endoplasmic reticulum translocon. Nature 433, 377-381.
76. Urban S, &, Freeman M, (2003) Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain. Mol Cell 11, 1425-1434.
77. Akiyama Y, &, Maegawa S, (2007) Sequence features of substrates required for cleavage by GlpG, an Escherichia coli rhomboid protease. Mol Microbiol 64, 1028-1037.
78. Maegawa S, Koide K, Ito K, &, Akiyama Y, (2007) The intramembrane active site of GlpG, an E. coli rhomboid protease, is accessible to water and hydrolyses an extramembrane peptide bond of substrates. Mol Microbiol 64, 435-447.
79. Strisovsky K, Sharpe HJ, &, Freeman M, (2009) Sequence-specific intramembrane proteolysis: identification of a recognition motif in rhomboid substrates. Mol Cell 36, 1048-1059.
80. Adrain C, Strisovsky K, Zettl M, Hu L, Lemberg MK, &, Freeman M, (2011) Mammalian EGF receptor activation by the rhomboid protease RHBDL2. EMBO Rep 12, 421-427.
81. Overall CM, (2002) Molecular determinants of metalloproteinase substrate specificity: matrix metalloproteinase substrate binding domains, modules, and exosites. Mol Biotechnol 22, 51-86.
82. Moin SM, &, Urban S, (2012) Membrane immersion allows rhomboid proteases to achieve specificity by reading transmembrane segment dynamics. Elife 1, e00173.
83. Ben-Shem A, Fass D, &, Bibi E, (2007) Structural basis for intramembrane proteolysis by rhomboid serine proteases. Proc Natl Acad Sci USA 104, 462-466.
84. Wu Z, Yan N, Feng L, Oberstein A, Yan H, Baker RP, Gu L, Jeffrey PD, Urban S, &, Shi Y, (2006) Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry. Nat Struct Mol Biol 13, 1084-1091.
85. Wang Y, Zhang Y, &, Ha Y, (2006) Crystal structure of a rhomboid family intramembrane protease. Nature 444, 179-180.
86. Lemieux MJ, Fischer SJ, Cherney MM, Bateman KS, &, James MN, (2007) The crystal structure of the rhomboid peptidase from Haemophilus influenzae provides insight into intramembrane proteolysis. Proc Natl Acad Sci USA 104, 750-754.
87. Baker RP, &, Urban S, (2012) Architectural and thermodynamic principles underlying intramembrane protease function. Nat Chem Biol 8, 759-768.
88. Vinothkumar KR, (2011) Structure of rhomboid protease in a lipid environment. J Mol Biol 407, 232-247.
89. Wang Y, &, Ha Y, (2007) Open-cap conformation of intramembrane protease GlpG. Proc Natl Acad Sci USA 104, 2098-2102.
90. Brooks CL, Lazareno-Saez C, Lamoureux JS, Mak MW, &, Lemieux MJ, (2011) Insights into substrate gating in H. influenzae rhomboid. J Mol Biol 407, 687-697.
91. Wang Y, Maegawa S, Akiyama Y, &, Ha Y, (2007) The role of L1 loop in the mechanism of rhomboid intramembrane protease GlpG. J Mol Biol 374, 1104-1113.
92. Bondar AN, del Val C, &, White SH, (2009) Rhomboid protease dynamics and lipid interactions. Structure 17, 395-405.
93. Baker RP, Young K, Feng L, Shi Y, &, Urban S, (2007) From the Cover: Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate. Proc Natl Acad Sci USA 104, 8257-8262.
94. Urban S, &, Baker RP, (2008) In vivo analysis reveals substrate-gating mutants of a rhomboid intramembrane protease display increased activity in living cells. Biol Chem 389, 1107-1115.
95. Vinothkumar KR, Strisovsky K, Andreeva A, Christova Y, Verhelst S, &, Freeman M, (2010) The structural basis for catalysis and substrate specificity of a rhomboid protease. EMBO J 29, 3797-3809.
96. Xue Y, Chowdhury S, Liu X, Akiyama Y, Ellman J, &, Ha Y, (2012) Conformational change in rhomboid protease GlpG induced by inhibitor binding to its S' subsites. Biochemistry 51, 3723-3731.
97. Xue Y, &, Ha Y, (2012) Catalytic mechanism of rhomboid protease GlpG probed by 3,4-dichloroisocoumarin and diisopropyl fluorophosphonate. J Biol Chem 287, 3099-3107.
98. Reddy T, &, Rainey JK, (2012) Multifaceted substrate capture scheme of a rhomboid protease. J Phys Chem B 116, 8942-8954.
99. Tyndall JD, Nall T, &, Fairlie DP, (2005) Proteases universally recognize beta strands in their active sites. Chem Rev 105, 973-999.
100. Perona JJ, &, Craik CS, (1995) Structural basis of substrate specificity in the serine proteases. Protein Sci 4, 337-360.
101. Hedstrom L, (2002) Serine protease mechanism and specificity. Chem Rev 102, 4501-4524.
102. Bode W, Meyer E, &, Powers JC, (1989) Human-leukocyte and porcine pancreatic elastase-X-ray crystal-structures, mechanism, substrate-specificity, and mechanism-based inhibitors. Biochemistry 28, 1951-1963.
103. Estell DA, Graycar TP, Miller JV, Powers DB, Wells JA, Burnier JP, &, Ng PG, (1986) Probing steric and hydrophobic effects on enzyme-substrate interactions by protein engineering. Science 233, 659-663.
104. Robertus JD, Kraut J, Alden RA, &, Birktoft JJ, (1972) Subtilisin; a stereochemical mechanism involving transition-state stabilization. Biochemistry 11, 4293-4303.
105. Pierrat OA, Strisovsky K, Christova Y, Large J, Ansell K, Bouloc N, Smiljanic E, &, Freeman M, (2011) Monocyclic beta-lactams are selective, mechanism-based inhibitors of rhomboid intramembrane proteases. ACS Chem Biol 6, 325-335.
106. Paetzel M, Dalbey RE, &, Strynadka NC, (1998) Crystal structure of a bacterial signal peptidase in complex with a beta-lactam inhibitor. Nature 396, 186-190.
107. Ekici ÖD, Paetzel M, &, Dalbey RE, (2008) Unconventional serine proteases: variations on the catalytic Ser/His/Asp triad configuration. Protein Sci 17, 2023-2037.
108. Zhou Y, Moin SM, Urban S, &, Zhang Y, (2012) An internal water-retention site in the rhomboid intramembrane protease GlpG ensures catalytic efficiency. Structure 20, 1255-1263.
109. Lei X, &, Li Y-M, (2009) The processing of human rhomboid intramembrane serine protease RHBDL2 is required for its proteolytic activity. J Mol Biol 394, 815-825.
110. Jeyaraju DV, McBride HM, Hill RB, &, Pellegrini L, (2011) Structural and mechanistic basis of Parl activity and regulation. Cell Death Differ 18, 1531-1539.
111. Yogev S, Schejter ED, &, Shilo BZ, (2008) Drosophila EGFR signalling is modulated by differential compartmentalization of Rhomboid intramembrane proteases. EMBO J 27, 1219-1230.
112. Yogev S, Schejter ED, &, Shilo BZ, (2010) Polarized secretion of Drosophila EGFR ligand from photoreceptor neurons is controlled by ER localization of the ligand-processing machinery. PLoS Biol 8, doi: 10.1371/journal.pbio.1000505.
113. Herlan M, (2004) Alternative topogenesis of Mgm1 and mitochondrial morphology depend on ATP and a functional import motor. J Cell Biol 165, 167-173.
114. Tatsuta T, Augustin S, Nolden M, Friedrichs B, &, Langer T, (2007) m-AAA protease-driven membrane dislocation allows intramembrane cleavage by rhomboid in mitochondria. EMBO J 26, 325-335.
115. Schafer A, Zick M, Kief J, Steger M, Heide H, Duvezin-Caubet S, Neupert W, &, Reichert AS, (2010) Intramembrane proteolysis of Mgm1 by the mitochondrial rhomboid protease is highly promiscuous regarding the sequence of the cleaved hydrophobic segment. J Mol Biol 401, 182-193.
116. Sherratt AR, Blais DR, Ghasriani H, Pezacki JP, &, Goto NK, (2012) Activity-based protein profiling of the Escherichia coli GlpG rhomboid protein delineates the catalytic core. Biochemistry 51, 7794-7803.
117. Sherratt AR, Braganza MV, Nguyen E, Ducat T, &, Goto NK, (2009) Insights into the effect of detergents on the full-length rhomboid protease from Pseudomonas aeruginosa and its cytosolic domain. Biochim Biophys Acta-Biomembranes 1788, 2444-2453.
118. Lazareno-Saez C, Arutyunova E, Coquelle N, &, Lemieux MJ, (2013) Domain swapping in the cytoplasmic domain of the Escherichia coli Rhomboid Protease. J Mol Biol, doi: 10.1016/j.jmb.2013.01.019.
119. Popot JL, &, Engelman DM, (2000) Helical membrane protein folding, stability, and evolution. Annu Rev Biochem 69, 881-922.
120. Kanehara K, (2002) YaeL (EcfE) activates the sigma E pathway of stress response through a site-2 cleavage of anti-sigma E. RseA. Genes Dev 16, 2147-2155.
121. Alba BM, Leeds JA, Onufryk C, Lu CZ, &, Gross CA, (2002) DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma(E)-dependent extracytoplasmic stress response. Genes Dev 16, 2156-2168.
122. Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, Brown MS, &, Goldstein JL, (2000) ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell 6, 1355-1364.
123. Rudner DZ, Fawcett P, &, Losick R, (1999) A family of membrane-embedded metalloproteases involved in regulated proteolysis of membrane-associated transcription factors. Proc Natl Acad Sci USA 96, 14765-14770.
124. Schobel S, Zellmeier S, Schumann W, &, Wiegert T, (2004) The Bacillus subtilis sigmaW anti-sigma factor RsiW is degraded by intramembrane proteolysis through YluC. Mol Microbiol 52, 1091-1105.
125. Sklar JG, Makinoshima H, Schneider JS, &, Glickman MS, (2010) M. tuberculosis intramembrane protease Rip1 controls transcription through three anti-sigma factor substrates. Mol Microbiol 77, 605-617.
126. Makinoshima H, &, Glickman MS, (2005) Regulation of Mycobacterium tuberculosis cell envelope composition and virulence by intramembrane proteolysis. Nature 436, 406-409.
127. Draper RC, Martin LW, Beare PA, &, Lamont IL, (2011) Differential proteolysis of sigma regulators controls cell-surface signalling in Pseudomonas aeruginosa. Mol Microbiol 82, 1444-1453.
128. Matson JS, &, DiRita VJ, (2005) Degradation of the membrane-localized virulence activator TcpP by the YaeL protease in Vibrio cholerae. Proc Natl Acad Sci USA 102, 16403-16408.
129. Qiu D, Eisinger VM, Rowen DW, &, Yu HD, (2007) Regulated proteolysis controls mucoid conversion in Pseudomonas aeruginosa. Proc Natl Acad Sci USA 104, 8107-8112.
130. King-Lyons ND, Smith KF, &, Connell TD, (2007) Expression of hurP, a gene encoding a prospective Site 2 protease. Is essential for heme-dependent induction of bhuR in Bordetella bronchiseptica. J Bacteriol 189, 6266-6275.
131. Saito A, Hizukuri Y, Matsuo E, Chiba S, Mori H, Nishimura O, Ito K, &, Akiyama Y, (2011) Post-liberation cleavage of signal peptides is catalyzed by the site-2 protease (S2P) in bacteria. Proc Natl Acad Sci USA 108, 13740-13745.
132. Feng L, Yan H, Wu Z, Yan N, Wang Z, Jeffrey PD, &, Shi Y, (2007) Structure of a Site-2 protease family intramembrane metalloprotease. Science 318, 1608-1612.
133. Koide K, Ito K, &, Akiyama Y, (2008) Substrate recognition and binding by RseP, an Escherichia coli intramembrane protease. J Biol Chem 283, 9562-9570.
134. Li X, Wang B, Feng L, Kang H, Qi Y, Wang J, &, Shi Y, (2009) Cleavage of RseA by RseP requires a carboxyl-terminal hydrophobic amino acid following DegS cleavage. Proc Natl Acad Sci USA 106, 14837-14842.
135. Zhou R, Cusumano C, Sui D, Garavito RM, &, Kroos L, (2009) Intramembrane proteolytic cleavage of a membrane-tethered transcription factor by a metalloprotease depends on ATP. Proc Natl Acad Sci USA 106, 16174-16179.
136. Wolfe MS, Citron M, Diehl TS, Xia W, Donkor IO, &, Selkoe DJ, (1998) A substrate-based difluoro ketone selectively inhibits Alzheimer's gamma-secretase activity. J Med Chem 41, 6-9.
137. Bardy SL, &, Jarrell KF, (2002) FlaK of the archaeon Methanococcus maripaludis possesses preflagellin peptidase activity. FEMS Microbiol Lett 208, 53-59.
138. Bardy SL, &, Jarrell KF, (2003) Cleavage of preflagellins by an aspartic acid signal peptidase is essential for flagellation in the archaeon Methanococcus voltae. Mol Microbiol 50, 1339-1347.
139. Kimberly WT, LaVoie MJ, Ostaszewski BL, Ye W, Wolfe MS, &, Selkoe DJ, (2003) Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci USA 100, 6382-6387.
140. Edbauer D, Winkler E, Regula JT, Pesold B, Steiner H, &, Haass C, (2003) Reconstitution of gamma-secretase activity. Nat Cell Biol 5, 486-488.
141. Fluhrer R, Steiner H, &, Haass C, (2009) Intramembrane proteolysis by signal peptide peptidases: a comparative discussion of GXGD-type aspartyl proteases. J Biol Chem 284, 13975-13979.
142. Narayanan S, Sato T, &, Wolfe MS, (2007) A C-terminal region of signal peptide peptidase defines a functional domain for intramembrane aspartic protease catalysis. J Biol Chem 282, 20172-20179.
143. Hu J, Xue Y, Lee S, &, Ha Y, (2011) The crystal structure of GXGD membrane protease FlaK. Nature 475, 528-531.
144. Li X, Dang S, Yan C, Gong X, Wang J, &, Shi Y, (2013) Structure of a presenilin family intramembrane aspartate protease. Nature 493, 56-61.
145. Sobhanifar S, Schneider B, Lohr F, Gottstein D, Ikeya T, Mlynarczyk K, Pulawski W, Ghoshdastider U, Kolinski M, Filipek S, et al,. (2010) Structural investigation of the C-terminal catalytic fragment of presenilin 1. Proc Natl Acad Sci USA 107, 9644-9649.
146. Osenkowski P, Li H, Ye W, Li D, Aeschbach L, Fraering PC, Wolfe MS, Selkoe DJ, &, Li H, (2009) Cryoelectron microscopy structure of purified gamma-secretase at 12 A resolution. J Mol Biol 385, 642-652.
147. Lazarov VK, Fraering PC, Ye W, Wolfe MS, Selkoe DJ, &, Li H, (2006) Electron microscopic structure of purified, active gamma-secretase reveals an aqueous intramembrane chamber and two pores. Proc Natl Acad Sci USA 103, 6889-6894.
148. Renzi F, Zhang X, Rice WJ, Torres-Arancivia C, Gomez-Llorente Y, Diaz R, Ahn K, Yu C, Li YM, Sisodia SS, et al,. (2011) Structure of gamma-secretase and its trimeric pre-activation intermediate by single-particle electron microscopy. J Biol Chem 286, 21440-21449.
149. Torres-Arancivia C, Ross CM, Chavez J, Assur Z, Dolios G, Mancia F, &, Ubarretxena-Belandia I, (2010) Identification of an archaeal presenilin-like intramembrane protease. PLoS One 5, doi: 10.1371/journal.pone. 0013072.
150. Ponting CP, Hutton M, Nyborg A, Baker M, Jansen K, &, Golde TE, (2002) Identification of a novel family of presenilin homologues. Hum Mol Genet 11, 1037-1044.
151. Podlisny MB, Citron M, Amarante P, Sherrington R, Xia W, Zhang J, Diehl T, Levesque G, Fraser P, Haass C, et al,. (1997) Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue. Neurobiol Dis 3, 325-337.
152. Thinakaran G, Borchelt DR, Lee MK, Slunt HH, Spitzer L, Kim G, Ratovitsky T, Davenport F, Nordstedt C, Seeger M, et al,. (1996) Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17, 181-190.
153. Tolia A, Horre K, &, De Strooper B, (2008) Transmembrane domain 9 of presenilin determines the dynamic conformation of the catalytic site of gamma-secretase. J Biol Chem 283, 19793-19803.
154. Tolia A, Chavez-Gutierrez L, &, De Strooper B, (2006) Contribution of presenilin transmembrane domains 6 and 7 to a water-containing cavity in the gamma-secretase complex. J Biol Chem 281, 27633-27642.
155. Sato C, Takagi S, Tomita T, &, Iwatsubo T, (2008) The C-terminal PAL motif and transmembrane domain 9 of presenilin 1 are involved in the formation of the catalytic pore of the gamma-secretase. J Neurosci 28, 6264-6271.
156. Shah S, Lee SF, Tabuchi K, Hao YH, Yu C, LaPlant Q, Ball H, Dann CE III, Sudhof T, &, Yu G, (2005) Nicastrin functions as a gamma-secretase-substrate receptor. Cell 122, 435-447.
157. Dries DR, Shah S, Han YH, Yu C, Yu S, Shearman MS, &, Yu G, (2009) Glu-333 of nicastrin directly participates in gamma-secretase activity. J Biol Chem 284, 29714-29724.
158. Zhang X, Hoey RJ, Lin G, Koide A, Leung B, Ahn K, Dolios G, Paduch M, Ikeuchi T, Wang R, et al,. (2012) Identification of a tetratricopeptide repeat-like domain in the nicastrin subunit of gamma-secretase using synthetic antibodies. Proc Natl Acad Sci USA 109, 8534-8539.
159. Kornilova AY, Bihel F, Das C, &, Wolfe MS, (2005) The initial substrate-binding site of gamma-secretase is located on presenilin near the active site. Proc Natl Acad Sci USA 102, 3230-3235.
160. Esler WP, Kimberly WT, Ostaszewski BL, Ye W, Diehl TS, Selkoe DJ, &, Wolfe MS, (2002) Activity-dependent isolation of the presenilin- gamma -secretase complex reveals nicastrin and a gamma substrate. Proc Natl Acad Sci USA 99, 2720-2725.
161. Bernsel A, Viklund H, Hennerdal A, &, Elofsson A, (2009) TOPCONS: consensus prediction of membrane protein topology. Nucleic Acids Res 37, W465-W468.
162. Zhou XW, Blackman MJ, Howell SA, &, Carruthers VB, (2004) Proteomic analysis of cleavage events reveals a dynamic two-step mechanism for proteolysis of a key parasite adhesive complex. Mol Cell Proteomics 3, 565-576.
163. O'Donnell RA, Hackett F, Howell SA, Treeck M, Struck N, Krnajski Z, Withers-Martinez C, Gilberger TW, &, Blackman MJ, (2006) Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite. J Cell Biol 174, 1023-1033.