Multispecific recognition: Mechanism, evolution, and design

Biochemistry

Volumn 50, Issue 5, 2011, Pages 602-611

  Erijman, Ariel ^a   Aizner, Yonatan ^a   Shifman, Julia M ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY-ANTIGEN; BASIC PRINCIPLES; BIOMEDICAL APPLICATIONS; COMPLEX PROCESSES; DIRECTED EVOLUTION; IMMUNE RESPONSE; METABOLIC NETWORK; MULTIPLE TARGETS; NOVEL PROTEINS; PROTEIN DESIGN; PROTEIN-PROTEIN COMPLEXES; REGULATION OF TRANSCRIPTION; SINGLE SEQUENCES; SMALL MOLECULES; T-CELL RECEPTORS;

CELL MEMBRANES; COMPLEXATION; PEPTIDES;

NUCLEIC ACIDS;

DNA; PROTEIN; T LYMPHOCYTE RECEPTOR;

ANTIGEN ANTIBODY REACTION; ARTICLE; ENZYME SUBSTRATE COMPLEX; HUMAN; MOLECULAR EVOLUTION; MOLECULAR INTERACTION; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN PROTEIN INTERACTION; RECEPTOR BINDING;

AMINO ACID SEQUENCE; ANIMALS; COMPUTATIONAL BIOLOGY; EVOLUTION, MOLECULAR; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN BINDING; PROTEINS; SPECIES SPECIFICITY;

EID: 79952093554     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi101563v     Document Type: Article

References (160)

1. (Pubitemid 32295017)
2. Uetz, P., Giot, L., Cagney, G., Mansfield, T. A., Judson, R. S., Knight, J. R., Lockshon, D., Narayan, V., Srinivasan, M., Pochart, P., Qureshi-Emili, A., Li, Y., Godwin, B., Conover, D., Kalbfleisch, T., Vijayadamodar, G., Yang, M., Johnston, M., Fields, S., and Rothberg, J. M. (2000) A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 403, 623-627. (Pubitemid 30103994)
3. Giot, L., Bader, J. S., Brouwer, C., Chaudhuri, A., Kuang, B., Li, Y., Hao, Y. L., Ooi, C. E., Godwin, B., Vitols, E., Vijayadamodar, G., Pochart, P., Machineni, H., Welsh, M., Kong, Y., Zerhusen, B., Malcolm, R., Varrone, Z., Collis, A., Minto, M., Burgess, S., McDaniel, L., Stimpson, E., Spriggs, F., Williams, J., Neurath, K., Ioime, N., Agee, M., Voss, E., Furtak, K., Renzulli, R., Aanensen, N., Carrolla, S., Bickelhaupt, E., Lazovatsky, Y., DaSilva, A., Zhong, J., Stanyon, C. A., Finley, R. L., Jr., White, K. P., Braverman, M., Jarvie, T., Gold, S., Leach, M., Knight, J., Shimkets, R. A., McKenna, M. P., Chant, J., and Rothberg, J. M. (2003) A protein interaction map of Drosophila melanogaster. Science 302, 1727-1736. (Pubitemid 37505730)
4. Ho, Y., Gruhler, A., Heilbut, A., Bader, G. D., Moore, L., Adams, S. L., Millar, A., Taylor, P., Bennett, K., Boutilier, K., Yang, L., Wolting, C., Donaldson, I., Schandorff, S., Shewnarane, J., Vo, M., Taggart, J., Goudreault, M., Muskat, B., Alfarano, C., Dewar, D., Lin, Z., Michalickova, K., Willems, A. R., Sassi, H., Nielsen, P. A., Rasmussen, K. J., Andersen, J. R., Johansen, L. E., Hansen, L. H., Jespersen, H., Podtelejnikov, A., Nielsen, E., Crawford, J., Poulsen, V., Sorensen, B. D., Matthiesen, J., Hendrickson, R. C., Gleeson, F., Pawson, T., Moran, M. F., Durocher, D., Mann, M., Hogue, C. W., Figeys, D., and Tyers, M. (2002) Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415, 180-183. (Pubitemid 34059520)
5. Gavin, A. C., Bosche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Schultz, J., Rick, J. M., Michon, A. M., Cruciat, C. M., Remor, M., Hofert, C., Schelder, M., Brajenovic, M., Ruffner, H., Merino, A., Klein, K., Hudak, M., Dickson, D., Rudi, T., Gnau, V., Bauch, A., Bastuck, S., Huhse, B., Leutwein, C., Heurtier, M. A., Copley, R. R., Edelmann, A., Querfurth, E., Rybin, V., Drewes, G., Raida, M., Bouwmeester, T., Bork, P., Seraphin, B., Kuster, B., Neubauer, G., and Superti-Furga, G. (2002) Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415, 141-147. (Pubitemid 34059510)
6. Gavin, A. C., Aloy, P., Grandi, P., Krause, R., Boesche, M., Marzioch, M., Rau, C., Jensen, L. J., Bastuck, S., Dumpelfeld, B., Edelmann, A., Heurtier, M. A., Hoffman, V., Hoefert, C., Klein, K., Hudak, M., Michon, A. M., Schelder, M., Schirle, M., Remor, M., Rudi, T., Hooper, S., Bauer, A., Bouwmeester, T., Casari, G., Drewes, G., Neubauer, G., Rick, J. M., Kuster, B., Bork, P., Russell, R. B., and Superti-Furga, G. (2006) Proteome survey reveals modularity of the yeast cell machinery. Nature 440, 631-636.
7. Stelzl, U., Worm, U., Lalowski, M., Haenig, C., Brembeck, F. H., Goehler, H., Stroedicke, M., Zenkner, M., Schoenherr, A., Koeppen, S., Timm, J., Mintzlaff, S., Abraham, C., Bock, N., Kietzmann, S., Goedde, A., Toksoz, E., Droege, A., Krobitsch, S., Korn, B., Birchmeier, W., Lehrach, H., and Wanker, E. E. (2005) A human protein-protein interaction network: A resource for annotating the proteome. Cell 122, 957-968. (Pubitemid 41345212)
8. Rual, J. F., Venkatesan, K., Hao, T., Hirozane-Kishikawa, T., Dricot, A., Li, N., Berriz, G. F., Gibbons, F. D., Dreze, M., Ayivi- Guedehoussou, N., Klitgord, N., Simon, C., Boxem, M., Milstein, S., Rosenberg, J., Goldberg, D. S., Zhang, L. V., Wong, S. L., Franklin, G., Li, S., Albala, J. S., Lim, J., Fraughton, C., Llamosas, E., Cevik, S., Bex, C., Lamesch, P., Sikorski, R. S., Vandenhaute, J., Zoghbi, H. Y., Smolyar, A., Bosak, S., Sequerra, R., Doucette- Stamm, L., Cusick, M. E., Hill, D. E., Roth, F. P., and Vidal, M. (2005) Towards a proteome-scale map of the human protein-protein interaction network. Nature 437, 1173-1178. (Pubitemid 41509356)
9. Barabasi, A. L., and Albert, R. (1999) Emergence of scaling in random networks. Science 286, 509-512.
10. Patil, A., Kinoshita, K., and Nakamura, H. (2010) Hub promiscuity in protein-protein interaction networks. Int. J. Mol. Sci. 11, 1930-1943.
11. Jeong, H., Mason, S. P., Barabasi, A. L., and Oltvai, Z. N. (2001) Lethality and centrality in protein networks. Nature 411, 41-42. (Pubitemid 32428180)
12. Fraser, H. B., Hirsh, A. E., Steinmetz, L. M., Scharfe, C., and Feldman, M. W. (2002) Evolutionary rate in the protein interaction network. Science 296, 750-752. (Pubitemid 34442006)
13. Jordan, I. K., Wolf, Y. I., and Koonin, E. V. (2003) No simple dependence between protein evolution rate and the number of protein-protein interactions: Only the most prolific interactors tend to evolve slowly. BMC Evol. Biol. 3, 1.
14. Wuchty, S. (2004) Evolution and topology in the yeast protein interaction network. Genome Res. 14, 1310-1314. (Pubitemid 39029227)
15. Kim, P. M., Lu, L. J., Xia, Y., and Gerstein, M. B. (2006) Relating three-dimensional structures to protein networks provides evolutionary insights. Science 314, 1938-1941. (Pubitemid 46026118)
16. Valdar, W. S. J., and Thornton, J. M. (2001) Protein-protein interfaces: Analysis of amino acid conservation in homodimers. Proteins 42, 108-124.
17. Copley, S. D. (2003) Enzymes with extra talents: Moonlighting functions and catalytic promiscuity. Curr. Opin. Chem. Biol. 7, 265-272. (Pubitemid 36514958)
18. Hult, K., and Berglund, P. (2007) Enzyme promiscuity: Mechanism and applications. Trends Biotechnol. 25, 231-238. (Pubitemid 46589665)
19. Nobeli, I., Favia, A. D., and Thornton, J. M. (2009) Protein promiscuity and its implications for biotechnology. Nat. Biotechnol. 27, 157-167.
20. Babtie, A., Tokuriki, N., and Hollfelder, F. (2010) What makes an enzyme promiscuous? Curr. Opin. Chem. Biol. 14, 200-207.
21. Khersonsky, O., and Tawfik, D. S. (2010) Enzyme promiscuity: A mechanistic and evolutionary perspective. Annu. Rev. Biochem. 79, 471-505.
22. D'Ari, R., and Casadesus, J. (1998) Underground metabolism. BioEssays 20, 181-186. (Pubitemid 28132113)
23. Kim, J., and Copley, S. D. (2007) Why metabolic enzymes are essential or nonessential for growth of Escherichia coli k12 on glucose. Biochemistry 46, 12501-12511. (Pubitemid 350060077)
24. Patrick, W. M., Quandt, E. M., Swartzlander, D. B., andMatsumura, I. (2007) Multicopy suppression underpins metabolic evolvability. Mol. Biol. Evol. 24, 2716-2722.
25. de Groot, M. J. L., van Berlo, R. J. P., van Winden, W. A., Verheijen, P. J. T., Reinders, M. J. T., and de Ridder, D. (2009) Metabolite and reaction inference based on enzyme specificities. Bioinformatics 25, 2975-2982.
26. Macchiarulo, A., Nobeli, I., and Thornton, J. M. (2004) Ligand selectivity and competition between enzymes in silico. Nat. Biotechnol. 22, 1039-1045. (Pubitemid 39014486)
27. Favia, A. D., Nobeli, I., Glaser, F., and Thornton, J. M. (2008) Molecular docking for substrate identification: The short-chain dehydrogenases/reductases. J. Mol. Biol. 375, 855-874.
28. Hermann, J. C., Ghanem, E., Li, Y. C., Raushel, F. M., Irwin, J. J., and Shoichet, B. K. (2006) Predicting substrates by docking highenergy interMEDiates to enzyme structures. J. Am. Chem. Soc. 128, 15882-15891. (Pubitemid 44894131)
29. Hermann, J. C., Marti-Arbona, R., Fedorov, A. A., Fedorov, E., Almo, S. C., Shoichet, B. K., and Raushel, F. M. (2007) Structurebased activity prediction for an enzyme of unknown function. Nature 448, 775-779. (Pubitemid 47266333)
30. Cameron, D. J., and Erlanger, B. F. (1977) Evidence for multispecificity of antibody molecules. Nature 268, 763-765. (Pubitemid 8157428)
31. Richards, F. F., Konigsberg, W. H., Rosenstein, R. W., and Varga, J. M. (1975) On the specificity of antibodies. Science 187, 130-137.
32. Mason, D. (1998) A very high level of crossreactivity is an essential feature of the T-cell receptor. Immunol. Today 19, 395-404. (Pubitemid 28392279)
33. Wing, M. G. (1995) The molecular basis for a polyspecific antibody. Clin. Exp. Immunol. 99, 313-315.
34. Wucherpfennig, K. W., Gagnon, E., Call, M. J., Huseby, E. S., and Call, M. E. (2010) Structural biology of the T-cell receptor: Insights into receptor assembly, ligand recognition, and initiation of signaling. Cold Spring Harbor Perspect. Biol. 2, a005140.
35. Wilson, D. B., Wilson, D. H., Schroder, K., Pinilla, C., Blondelle, S., Houghten, R. A., and Garcia, K. C. (2004) Specificity and degeneracy of T cells. Mol. Immunol. 40, 1047-1055. (Pubitemid 38221185)
36. Kranz, D. M. (2000) Incompatible differences: View of an allogeneic pMHC-TCR complex. Nat. Immunol. 1, 277-278.
37. Chow, D. A., and Bennet, R. D. (1989) Low natural antibody and low in vivo tumor resistance, in xid-bearing B-cell deficient mice. J. Immunol. 142, 3702-3706. (Pubitemid 19137509)
38. Sethi, D. K., Agarwal, A., Manivel, V., Rao, K. V. S., and Salunke, D. M. (2006) Differential Epitope Positioning within the Germline Antibody Paratope Enhances Promiscuity in the Primary Immune Response. Immunity 24, 429-438.
39. Zimmermann, J., Oakman, E. L., Thorpe, I. F., Shi, X., Abbyad, P., Brooks, C. L., III, Boxer, S. G., and Romesberg, F. E. (2006) Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics. Proc. Natl. Acad. Sci. U.S.A. 103, 13722-13727. (Pubitemid 44413974)
40. Roggenbuck, D., Konig, H., Niemann, B., Schoenherr, G., Jahn, S., and Porstmann, T. (1994) Real-time biospecific interaction analysis of a natural human polyreactive monoclonal IgM antibody and its Fab and scFv fragments with several antigens. Scand. J. Immunol. 40, 64-70. (Pubitemid 24251723)
41. Poncet, P., Matthes, T., Billecocq, A., and Dighiero, G. (1988) Immunochemical studies of polyspecific natural autoantibodies: Charge, lipid reactivity, Fab′2 fragments activity and complement fixation. Mol. Immunol. 25, 981-989.
42. Bostrom, J., Yu, S. F., Kan, D., Appleton, B. A., Lee, C. V., Billeci, K., Man, W., Peale, F., Ross, S., Wiesmann, C., and Fuh, G. (2009) Variants of the Antibody Herceptin That Interact with HER2 and VEGF at the Antigen Binding Site. Science 323, 1610-1614.
43. Mariuzza, R. A. (2006) Multiple paths to multispecificity. Immunity 24, 359-361.
44. Badis, G., Berger, M. F., Philippakis, A. A., Talukder, S., Gehrke, A. R., Jaeger, S. A., Chan, E. T., Metzler, G., Vedenko, A., Chen, X., Kuznetsov, H., Wang, C.-F., Coburn, D., Newburger, D. E., Morris, Q., Hughes, T. R., and Bulyk, M.L. Diversity andcomplexity in DNA recognition by transcription factors. Science 2009, 324, 1720-1723
45. Bobay, B. G., Benson, L., Naylor, S., Feeney, B., Clark, A. C., Goshe, M. B., Strauch, M. A., Thompson, R., and Cavanagh, J. (2004) Evaluation of the DNA binding tendencies of the transition state regulator AbrB. Biochemistry 43, 16106-16118. (Pubitemid 40041024)
46. Ishii, A., and Hihara, Y. (2008) An AbrB-like transcriptional regulator, Sll0822, is essential for the activation of nitrogen-regulated genes in Synechocystis sp. PCC 6803. Plant Physiol. 148, 660-670. (Pubitemid 352847624)
47. Sullivan, D. M., Bobay, B. G., Kojetin, D. J., Thompson, R. J., Rance, M., Strauch, M. A., and Cavanagh, J. (2008) Insights into the Nature of DNA Binding of AbrB-like Transcription Factors. Structure 16, 1702-1713.
48. Kalodimos, C. G., Biris, N., Bonvin, A., Levandoski, M. M., Guennuegues, M., Boelens, R., and Kaptein, R. (2004) Structure and flexibility adaptation in nonspecific and specific protein-DNA complexes. Science 305, 386-389. (Pubitemid 38938152)
49. Vonhippel, P. H., and Berg, O. G. (1989) Facilitates target location in biological systems. J. Biol. Chem. 264, 675-678. (Pubitemid 19038039)
50. Halford, S. E., and Marko, J. F. (2004) How do site-specific DNAbinding proteins find their targets? Nucleic Acids Res. 32, 3040-3052. (Pubitemid 39022995)
51. Viadiu, H., and Aggarwal, A. K. (2000) Structure of BamHI bound to nonspecific DNA:Amodel forDNAsliding. Mol. Cell 5, 889-895.
52. Townson, S. A., Samuelson, J. C., Bao, Y. M., Xu, S. Y., and Aggarwal, A. K. (2007) BstYI bound to noncognate DNA reveals a "hemispecific" complex: Implications for DNA scanning. Structure 15, 449-459. (Pubitemid 46551729)
53. Walter, J., Trautner, T. A., and Noyer-Weidner, M. (1992) High plasticity of multispecific DNA methyltransferases in the region carrying DNA target recognizing enzyme modules. EMBO J. 11, 4445-4450.
54. James, L. C., and Tawfik, D. S. (2003) Conformational diversity and protein evolution: A 60-year-old hypothesis revisited. Trends Biochem. Sci. 28, 361-368. (Pubitemid 36851617)
55. Patil, A., and Nakamura, H. (2007) The role of charged surface residues in the binding ability of small hubs in protein-protein interaction networks. Biophysics 3, 27.
56. Iwahara, J., Zweckstetter, M., and Clore, G. M. (2006) NMR structural and kinetic characterization of a homeodomain diffusing and hopping on nonspecific DNA. Proc. Natl. Acad. Sci. U.S.A. 103, 15062-15067. (Pubitemid 44583164)
57. Fromer, M., and Shifman, J. M. (2009) Tradeoff between stability and multispecificity in the design of promiscuous proteins. PLoS Comput. Biol. 5, e1000627.
58. Lange, O. F., Lakomek, N. A., Fares, C., Schroder, G. F., Walter, K. F., Becker, S., Meiler, J., Grubmuller, H., Griesinger, C., and de Groot, B. L. (2008) Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution. Science 320, 1471-1475. (Pubitemid 351929422)
59. James, L. C., Roversi, P., and Tawfik, D. S. (2003) Antibody multispecificity MEDiated by conformational diversity. Science 299, 1362-1367. (Pubitemid 36254643)
60. Armstrong, K. M., Piepenbrink, K. H., and Baker, B. M. (2008) Conformational changes and flexibility in T-cell receptor recognition of peptide-MHC complexes. Biochem. J. 415, 183-196.
61. Patil, A., and Nakamura, H. (2006) Disordered domains and high surface charge confer hubs with the ability to interact with multiple proteins in interaction networks. FEBS Lett. 580, 2041-2045.
62. Kim, P. M., Sboner, A., Xia, Y., and Gerstein, M. (2008) The role of disorder in interaction networks: A structural analysis. Mol. Syst. Biol. 4, 179. (Pubitemid 351441045)
63. Dunker, A. K., Lawson, J. D., Brown, C. J., Williams, R. M., Romero, P., Oh, J. S., Oldfield, C. J., Campen, A. M., Ratliff, C. M., Hipps, K. W., Ausio, J., Nissen, M. S., Reeves, R., Kang, C., Kissinger, C. R., Bailey, R. W., Griswold, M. D., Chiu, W., Garner, E. C., and Obradovic, Z. 2001. Intrinsically disordered protein J. Mol. Graphics Modell. 19, 26-59. (Pubitemid 32411501)
64. Uversky, V. N., Oldfield, C. J., and Dunker, A. K. (2005) Showing your ID: Intrinsic disorder as an ID for recognition, regulation and cell signaling. J. Mol. Recognit. 18, 343-384. (Pubitemid 41341287)
65. Obradovic, Z., Peng, K., Vucetic, S., Radivojac, P., Brown, C. J., and Dunker, A. K. (2003) Predicting intrinsic disorder from amino acid sequence. Proteins 53 (Suppl. 6), 566-572. (Pubitemid 37352217)
66. Dunker, A. K., Cortese, M. S., Romero, P., Iakoucheva, L. M., and Uversky, V. N. (2005) Flexible nets. The roles of intrinsic disorder in protein interaction networks. FEBS J. 272, 5129-5148. (Pubitemid 41503146)
67. Wright, P. E., and Dyson, H. J. (1999) Intrinsically unstructured proteins: Re-assessing the protein structure-function paradigm. J. Mol. Biol. 293, 321-331. (Pubitemid 29516173)
68. Gsponer, J., Futschik, M. E., Teichmann, S. A., and Babu, M. M. (2008) Tight regulation of unstructured proteins: From transcript synthesis to protein degradation. Science 322, 1365-1368. (Pubitemid 352775246)
69. Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., and Whitelaw, M. L. (2002) Asparagine hydroxylation of the HIF transactivation domain: A hypoxic switch. Science 295, 858-861. (Pubitemid 34118367)
70. Elkins, J. M., Hewitson, K. S., McNeill, L. A., Seibel, J. r. F., Schlemminger, I., Pugh, C. W., Ratcliffe, P. J., and Schofield, C. J. (2003) Structure of Factor-inhibiting Hypoxia-inducible Factor 23.
71. Kim, J., and Copley, S. D. (2007) Why metabolic enzymes are essential or nonessential for growth of Escherichia coli k12 on glucose. Biochemistry 46, 12501-12511. (Pubitemid 350060077)
72. Patrick, W. M., Quandt, E. M., Swartzlander, D. B., andMatsumura, I. (2007) Multicopy suppression underpins metabolic evolvability. Mol. Biol. Evol. 24, 2716-2722.
73. de Groot, M. J. L., van Berlo, R. J. P., van Winden, W. A., Verheijen, P. J. T., Reinders, M. J. T., and de Ridder, D. (2009) Metabolite and reaction inference based on enzyme specificities. Bioinformatics 25, 2975-2982.
74. Macchiarulo, A., Nobeli, I., and Thornton, J. M. (2004) Ligand selectivity and competition between enzymes in silico. Nat. Biotechnol. 22, 1039-1045. (Pubitemid 39014486)
75. Favia, A. D., Nobeli, I., Glaser, F., and Thornton, J. M. (2008) Molecular docking for substrate identification: The short-chain dehydrogenases/reductases. J. Mol. Biol. 375, 855-874.
76. Hermann, J. C., Ghanem, E., Li, Y. C., Raushel, F. M., Irwin, J. J., and Shoichet, B. K. (2006) Predicting substrates by docking highenergy interMEDiates to enzyme structures. J. Am. Chem. Soc. 128, 15882-15891. (Pubitemid 44894131)
77. Hermann, J. C., Marti-Arbona, R., Fedorov, A. A., Fedorov, E., Almo, S. C., Shoichet, B. K., and Raushel, F. M. (2007) Structurebased activity prediction for an enzyme of unknown function. Nature 448, 775-779. (Pubitemid 47266333)
78. Cameron, D. J., and Erlanger, B. F. (1977) Evidence for multispecificity of antibody molecules. Nature 268, 763-765. (Pubitemid 8157428)
79. Richards, F. F., Konigsberg, W. H., Rosenstein, R. W., and Varga, J. M. (1975) On the specificity of antibodies. Science 187, 130-137.
80. Mason, D. (1998) A very high level of crossreactivity is an essential feature of the T-cell receptor. Immunol. Today 19, 395-404. (Pubitemid 28392279)
81. Wing, M. G. (1995) The molecular basis for a polyspecific antibody. Clin. Exp. Immunol. 99, 313-315.
82. Wucherpfennig, K. W., Gagnon, E., Call, M. J., Huseby, E. S., and Call, M. E. (2010) Structural biology of the T-cell receptor: Insights into receptor assembly, ligand recognition, and initiation of signaling. Cold Spring Harbor Perspect. Biol. 2, a005140.
83. Wilson, D. B., Wilson, D. H., Schroder, K., Pinilla, C., Blondelle, S., Houghten, R. A., and Garcia, K. C. (2004) Specificity and degeneracy of T cells. Mol. Immunol. 40, 1047-1055. (Pubitemid 38221185)
84. Kranz, D. M. (2000) Incompatible differences: View of an allogeneic pMHC-TCR complex. Nat. Immunol. 1, 277-278.
85. Chow, D. A., and Bennet, R. D. (1989) Low natural antibody and low in vivo tumor resistance, in xid-bearing B-cell deficient mice. J. Immunol. 142, 3702-3706. (Pubitemid 19137509)
86. Sethi, D. K., Agarwal, A., Manivel, V., Rao, K. V. S., and Salunke, D. M. (2006) Differential Epitope Positioning within the Germline Antibody Paratope Enhances Promiscuity in the Primary Immune Response. Immunity 24, 429-438.
87. Zimmermann, J., Oakman, E. L., Thorpe, I. F., Shi, X., Abbyad, P., Brooks, C. L., III, Boxer, S. G., and Romesberg, F. E. (2006) Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics. Proc. Natl. Acad. Sci. U.S.A. 103, 13722-13727. (Pubitemid 44413974)
88. Roggenbuck, D., Konig, H., Niemann, B., Schoenherr, G., Jahn, S., and Porstmann, T. (1994) Real-time biospecific interaction analysis of a natural human polyreactive monoclonal IgM antibody and its Fab and scFv fragments with several antigens. Scand. J. Immunol. 40, 64-70. (Pubitemid 24251723)
89. Poncet, P., Matthes, T., Billecocq, A., and Dighiero, G. (1988) Immunochemical studies of polyspecific natural autoantibodies: Charge, lipid reactivity, Fab′2 fragments activity and complement fixation. Mol. Immunol. 25, 981-989.
90. Bostrom, J., Yu, S. F., Kan, D., Appleton, B. A., Lee, C. V., Billeci, K., Man, W., Peale, F., Ross, S., Wiesmann, C., and Fuh, G. (2009) Variants of the Antibody Herceptin That Interact with HER2 and VEGF at the Antigen Binding Site. Science 323, 1610-1614.
91. Mariuzza, R. A. (2006) Multiple paths to multispecificity. Immunity 24, 359-361.
92. Badis, G., Berger, M. F., Philippakis, A. A., Talukder, S., Gehrke, A. R., Jaeger, S. A., Chan, E. T., Metzler, G., Vedenko, A., Chen, X., Kuznetsov, H., Wang, C.-F., Coburn, D., Newburger, D. E., Morris, Q., Hughes, T. R., and Bulyk, M.L. (2009)Diversity andComplexity in DNA Recognition by Transcription Factors. Science 324, 1720-1723.
93. Bobay, B. G., Benson, L., Naylor, S., Feeney, B., Clark, A. C., Goshe, M. B., Strauch, M. A., Thompson, R., and Cavanagh, J. (2004) Evaluation of the DNA binding tendencies of the transition state regulator AbrB. Biochemistry 43, 16106-16118. (Pubitemid 40041024)
94. Ishii, A., and Hihara, Y. (2008) An AbrB-like transcriptional regulator, Sll0822, is essential for the activation of nitrogen-regulated genes in Synechocystis sp. PCC 6803. Plant Physiol. 148, 660-670. (Pubitemid 352847624)
95. Sullivan, D. M., Bobay, B. G., Kojetin, D. J., Thompson, R. J., Rance, M., Strauch, M. A., and Cavanagh, J. (2008) Insights into the Nature of DNA Binding of AbrB-like Transcription Factors. Structure 16, 1702-1713.
96. Kalodimos, C. G., Biris, N., Bonvin, A., Levandoski, M. M., Guennuegues, M., Boelens, R., and Kaptein, R. (2004) Structure and flexibility adaptation in nonspecific and specific protein-DNA complexes. Science 305, 386-389. (Pubitemid 38938152)
97. Vonhippel, P. H., and Berg, O. G. (1989) Facilitates target location in biological systems. J. Biol. Chem. 264, 675-678. (Pubitemid 19038039)
98. Halford, S. E., and Marko, J. F. (2004) How do site-specific DNAbinding proteins find their targets? Nucleic Acids Res. 32, 3040-3052. (Pubitemid 39022995)
99. Viadiu, H., and Aggarwal, A. K. (2000) Structure of BamHI bound to nonspecific DNA:Amodel forDNAsliding. Mol. Cell 5, 889-895.
100. Townson, S. A., Samuelson, J. C., Bao, Y. M., Xu, S. Y., and Aggarwal, A. K. (2007) BstYI bound to noncognate DNA reveals a "hemispecific" complex: Implications for DNA scanning. Structure 15, 449-459. (Pubitemid 46551729)
101. Walter, J., Trautner, T. A., and Noyer-Weidner, M. (1992) High plasticity of multispecific DNA methyltransferases in the region carrying DNA target recognizing enzyme modules. EMBO J. 11, 4445-4450.
102. James, L. C., and Tawfik, D. S. (2003) Conformational diversity and protein evolution: A 60-year-old hypothesis revisited. Trends Biochem. Sci. 28, 361-368. (Pubitemid 36851617)
103. Patil, A., and Nakamura, H. (2007) The role of charged surface residues in the binding ability of small hubs in protein-protein interaction networks. Biophysics 3, 27.
104. Iwahara, J., Zweckstetter, M., and Clore, G. M. (2006) NMR structural and kinetic characterization of a homeodomain diffusing and hopping on nonspecific DNA. Proc. Natl. Acad. Sci. U.S.A. 103, 15062-15067. (Pubitemid 44583164)
105. Fromer, M., and Shifman, J. M. (2009) Tradeoff between stability and multispecificity in the design of promiscuous proteins. PLoS Comput. Biol. 5, e1000627.
106. Lange, O. F., Lakomek, N. A., Fares, C., Schroder, G. F., Walter, K. F., Becker, S., Meiler, J., Grubmuller, H., Griesinger, C., and de Groot, B. L. (2008) Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution. Science 320, 1471-1475. (Pubitemid 351929422)
107. James, L. C., Roversi, P., and Tawfik, D. S. (2003) Antibody multispecificity MEDiated by conformational diversity. Science 299, 1362-1367. (Pubitemid 36254643)
108. Armstrong, K. M., Piepenbrink, K. H., and Baker, B. M. (2008) Conformational changes and flexibility in T-cell receptor recognition of peptide-MHC complexes. Biochem. J. 415, 183-196.
109. Patil, A., and Nakamura, H. (2006) Disordered domains and high surface charge confer hubs with the ability to interact with multiple proteins in interaction networks. FEBS Lett. 580, 2041-2045.
110. Kim, P. M., Sboner, A., Xia, Y., and Gerstein, M. (2008) The role of disorder in interaction networks: A structural analysis. Mol. Syst. Biol. 4, 179. (Pubitemid 351441045)
111. Dunker, A. K., Lawson, J. D., Brown, C. J., Williams, R. M., Romero, P., Oh, J. S., Oldfield, C. J., Campen, A. M., Ratliff, C. M., Hipps, K. W., Ausio, J., Nissen, M. S., Reeves, R., Kang, C., Kissinger, C. R., Bailey, R. W., Griswold, M. D., Chiu, W., Garner, E. C., and Obradovic, Z. (2001) Intrinsically disordered protein. J. Mol. Graphics Modell. 19, 26-59. (Pubitemid 32411501)
112. Uversky, V. N., Oldfield, C. J., and Dunker, A. K. (2005) Showing your ID: Intrinsic disorder as an ID for recognition, regulation and cell signaling. J. Mol. Recognit. 18, 343-384. (Pubitemid 41341287)
113. Obradovic, Z., Peng, K., Vucetic, S., Radivojac, P., Brown, C. J., and Dunker, A. K. (2003) Predicting intrinsic disorder from amino acid sequence. Proteins 53 (Suppl. 6), 566-572. (Pubitemid 37352217)
114. Dunker, A. K., Cortese, M. S., Romero, P., Iakoucheva, L. M., and Uversky, V. N. (2005) Flexible nets. The roles of intrinsic disorder in protein interaction networks. FEBS J. 272, 5129-5148. (Pubitemid 41503146)
115. Wright, P. E., and Dyson, H. J. (1999) Intrinsically unstructured proteins: Re-assessing the protein structure-function paradigm. J. Mol. Biol. 293, 321-331. (Pubitemid 29516173)
116. Gsponer, J., Futschik, M. E., Teichmann, S. A., and Babu, M. M. (2008) Tight regulation of unstructured proteins: From transcript synthesis to protein degradation. Science 322, 1365-1368. (Pubitemid 352775246)
117. Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., and Whitelaw, M. L. (2002) Asparagine hydroxylation of the HIF transactivation domain: A hypoxic switch. Science 295, 858-861. (Pubitemid 34118367)
118. Elkins, J. M., Hewitson, K. S., McNeill, L. A., Seibel, J. r. F., Schlemminger, I., Pugh, C. W., Ratcliffe, P. J., and Schofield, C. J. (2003) Structure of Factor-inhibiting Hypoxia-inducible Factor (HIF) Reveals Mechanism of Oxidative Modification of HIF-1R. J. Biol. Chem. 278, 1802-1806. (Pubitemid 36801416)
119. Merkley, N., and Shaw, G. S. (2004) Solution structure of the flexible class II ubiquitin-conjugating enzyme Ubc1 provides insights for polyubiquitin chain assembly. J. Biol. Chem. 279, 47139-47147. (Pubitemid 39523129)
120. 2+-bound calmodulin: An analysis of disorder and implications for functionally relevant plasticity. J. Mol. Biol. 301, 1237-1256.
121. Goodman, R. H., and Smolik, S. (2000) CBP/p300 in cell growth, transformation, and development. Genes Dev. 14, 1553-1577. (Pubitemid 30460905)
122. Parker, D., Rivera, M., Zor, T., Henrion-Caude, A., Radhakrishnan, I., Kumar, A., Shapiro, L. H., Wright, P. E., Montminy, M., and Brindle, P. K. (1999) Role of secondary structure in discrimination between constitutive and inducible activators. Mol. Cell. Biol. 19, 5601-5607. (Pubitemid 29339917)
123. Radhakrishnan, I., Perez-Alvarado, G. C., Parker, D., Dyson, H. J., Montminy, M. R., and Wright, P. E. (1997) Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: A model for activator:coactivator interactions. Cell 91, 741-752. (Pubitemid 28007731)
124. Kim, T. D., Paik, S. R., and Yang, C. H. (2002) Structural and functional implications of C-terminal regions of R-synuclein. Biochemistry 41, 13782-13790. (Pubitemid 35332716)
125. Park, S. M., Jung, H. Y., Kim, T. D., Park, J. H., Yang, C. H., and Kim, J. (2002) Distinct roles of the N-terminal-binding domain and the C-terminal-solubilizing domain of R-synuclein, a molecular chaperone. J. Biol. Chem. 277, 28512-28520. (Pubitemid 41079277)
126. Bhattacharyya, J., and Das, K. P. (1999) Molecular chaperone-like properties of an unfolded protein, R(s)-casein. J. Biol. Chem. 274, 15505-15509.
127. Smulders, R., Carver, J. A., Lindner, R. A., van Boekel, M. A., Bloemendal, H., and de Jong, W. W. (1996) Immobilization of the C-terminal extension of bovine RA-crystallin reduces chaperone-like activity. J. Biol. Chem. 271, 29060-29066. (Pubitemid 26382612)
128. Pasta, S. Y., Raman, B., Ramakrishna, T., and Rao, Ch. M. (2002) Role of the C-terminal extensions of R-crystallins. Swapping the C-terminal extension of R-Crystallin to RB-Crystallin results in enhanced chaperone activity. J. Biol. Chem. 277, 45821-45828. (Pubitemid 35417560)
129. Lindner, R. A., Carver, J. A., Ehrnsperger, M., Buchner, J., Esposito, G., Behlke, J., Lutsch, G., Kotlyarov, A., and Gaestel, M. (2000) MouseHsp25, a small shock protein. The role of its C-terminal extension in oligomerization and chaperone action. Eur. J. Biochem. 267, 1923-1932. (Pubitemid 30185278)
130. Tompa, P., and Csermely, P. (2004) The role of structural disorder in the function of RNA and protein chaperones. FASEB J. 18, 1169-1175. (Pubitemid 39006878)
131. Ikura, M., and Ames, J. B. (2006) Genetic polymorphism and protein conformational plasticity in the calmodulin superfamily: Two ways to promote multifunctionality. Proc. Natl. Acad. Sci. U.S.A. 103, 1159-1164. (Pubitemid 43191135)
132. Friedler, A., Veprintsev, D. B., Rutherford, T., von Glos, K. I., and Fersht, A. R. (2005) Binding of Rad51 and other peptide sequences to a promiscuous, highly electrostatic binding site in p53. J. Biol. Chem. 280, 8051-8059. (Pubitemid 40349703)
133. Sheinerman, F. B., Norel, R., andHonig, B. (2000) Electrostatic aspects of protein-protein interactions. Curr. Opin. Struct. Biol. 10, 153-159. (Pubitemid 30198940)
134. Schreiber, G., and Fersht, A. R. (1996) Rapid, electrostatically assisted association of proteins. Nat. Struct. Biol. 3, 427-431. (Pubitemid 26139441)
135. Rajamani, D., Thiel, S., Vajda, S., and Camacho, C. J. (2004) Anchor residues in protein-protein interactions. Proc. Natl. Acad. Sci. U.S.A. 101, 11287-11292. (Pubitemid 39038339)
136. Fields, B.A., Goldbaum, F.A., Ysern, X., Poljak, R. J., andMariuzza, R. A. (1995) Molecular basis of antigen mimicry by an anti-idiotope. Nature 374, 739-742.
137. McFarland, B. J., Kortemme, T., Yu, S. F., Baker, D., and Strong, R. K. (2003) Symmetry recognizing asymmetry: Analysis of the interactions between the C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands. Structure 11, 411-422. (Pubitemid 36419568)
138. Watkins, R. E., Wisely, G. B., Moore, L. B., Collins, J. L., Lambert, M. H., Williams, S. P., Willson, T. M., Kliewer, S. A., and Redinbo, M. R. (2001) The human nuclear xenobiotic receptor PXR: Structural determinants of directed promiscuity. Science 292, 2329-2333. (Pubitemid 32568055)
139. Ngan, C.-H., Beglov, D., Rudnitskaya, A. N., Kozakov, D., Waxman, D. J., and Vajda, S. (2009) The StructuralBasis of PregnaneXReceptor Binding Promiscuity. Biochemistry 48, 11572-11581.
140. Tsai, C. J., Ma, B., and Nussinov, R. (2009) Protein-protein interaction networks: How can a hub protein bind so many different partners? Trends Biochem. Sci. 34, 594-600.
141. Larion, M., Moore, L. B., Thompson, S. M., and Miller, B. G. (2007) Divergent evolution of function in the ROK sugar kinase superfamily: Role of enzyme loops in substrate specificity. Biochemistry 46, 13564-13572. (Pubitemid 350209952)
142. Matsumura, I., and Ellington, A. D. (2001) In vitro evolution of β-glucuronidase into a β-galactosidase proceeds through non-specific interMEDiates. J. Mol. Biol. 305, 331-339. (Pubitemid 32099464)
143. Jensen, R. A. (1976) Enzyme Recruitment in Evolution of New Function. Annu. Rev. Microbiol. 30, 409-425.
144. Levin, K. B., Dym, O., Albeck, S., Magdassi, S., Keeble, A. H., Kleanthous, C., and Tawfik, D. S. (2009) Following evolutionary paths to protein-protein interactions with high affinity and selectivity. Nat. Struct. Mol. Biol. 16, 1049-1067.
145. Collins, C. H., Arnold, F. H., and Leadbetter, J. R. (2005) Directed evolution of Vibrio fischeri LuxR for increased sensitivity to a broad spectrum of acyl-homoserine lactones. Mol. Microbiol. 55, 712-723. (Pubitemid 40203688)
146. Collins, C. H., Leadbetter, J. R., and Arnold, F. H. (2006) Dual selection enhances the signaling specificity of a variant of the quorumsensing transcriptional activator LuxR. Nat. Biotechnol. 24, 708-712. (Pubitemid 43882123)
147. Aharoni, A., Gaidukov, L., Khersonsky, O., Gould, S.M., Roodveldt, C.,
148. Tokuriki, N., and Tawfik, D. S. (2009) Protein Dynamism and Evolvability. Science 324, 203-207.
149. Vedha-Peters, K., Gunawardana, M., Rozzell, J. D., and Novick, S. J. (2006) Creation of a broad-range and highly stereoselective D-amino acid dehydrogenase for the one-step synthesis of D-amino acids. J. Am. Chem. Soc. 128, 10923-10929. (Pubitemid 44277779)
150. Allen, B. D., and Mayo, S. L. (2010) An efficient algorithm for multistate protein design based on FASTER. J. Comput. Chem. 31, 904-916.
151. Fromer, M., Yanover, C., and Linial, M. (2010) Design of multispecific protein sequences using probabilistic graphical modeling. Proteins 78, 530-547.
152. Humphris, E. L., and Kortemme, T. (2007) Design of multi-specificity in protein interfaces. PLoS Comput. Biol. 3, e164.
153. Yanover, C., Fromer, M., and Shifman, J. M. (2007) Dead-end elimination for multistate protein design. J. Comput. Chem. 28, 2122-2129. (Pubitemid 47265250)
154. Fromer, M., Yanover, C., Harel, A., Shachar, O., Weiss, Y., and Linial, M. (2010) SPRINT: Side-chain Prediction Inference Toolbox for Multistate Protein Design. Bioinformatics 26, 2466-2467.
155. Shifman, J. M., and Mayo, S. L. (2003) Exploring the origins of binding specificity through the computational redesign of calmodulin. Proc. Natl. Acad. Sci. U.S.A. 100, 13274-13279. (Pubitemid 37444732)
156. Yosef, E., Politi, R., Choi, M. H., and Shifman, J. M. (2009) Computational design of calmodulin mutants with up to 900-fold increase in binding specificity. J. Mol. Biol. 385, 1470-1480.
157. 2+indicators based on computationally redesigned calmodulin-peptide pairs. Chem. Biol. 13, 521-530. (Pubitemid 43729506)
158. Suarez, M., Tortosa, P., Carrera, J., and Jaramillo, A. (2008) Pareto optimization in computational protein design with multiple objectives. J. Comput. Chem. 29, 2704-2711.
159. Suarez, M., Tortosa, P., Garcia-Mira, M. M., Rodriguez-Larrea, D., Godoy-Ruiz, R., Ibarra-Molero, B., Sanchez-Ruiz, J. M., and Jaramillo, A. (2010) Using multi-objective computational design to extend protein promiscuity. Biophys. Chem. 147, 13-19.
160. DeLano, W. L. (2008) The PyMOL Molecular Graphics System, DeLano Scientific, Palo Alto, CA.