全新设计蛋白质的折叠机制

doi:10.3866/PKU.WHXB201209144

摘要/Abstract

摘要：

蛋白质全新设计和折叠研究是从两个不同的方向来理解蛋白质序列-结构-功能关系这一结构生物学重要问题. 蛋白质全新设计取得的成功实例一定程度上检验了人们对蛋白质结构和相互作用理解的准确性, 但它们中多数所表现的不同于天然蛋白质的折叠动力学特征也表明, 要达到最终的功能化实现目标还面临着不少的挑战. 本文综述了蛋白质全新设计的发展过程及现状, 蛋白质折叠研究在实验、理论及模拟方面的研究进展, 以及全新设计蛋白质的折叠机制的研究现状. 阐述了深入了解全新设计蛋白质与天然蛋白质折叠机制的不同, 可以为进一步有效地合理化设计蛋白质提供有益的参考.

关键词: 蛋白质全新设计, 蛋白质折叠, 目标结构, 折叠动力学特征

Abstract:

Protein de novo design and protein folding are two different means to investigate“sequencestructure- function”relationship of proteins, which is one of the most important focuses in structural biology. The successful achievements in protein de novo design indicate the understanding accuracy of the knowledge in protein structure and interaction, while most of those designed proteins show different folding kinetic features from nature occurring proteins, which implies that there are still many challenges to the aim of getting them to play expected biological function. In this review, the status of research and development for protein de novo design, as well as the study progress of protein folding in experimental, theoretical and simulation aspects, have been introduced. Further, the investigations of folding mechanism of de novo designed proteins have been reviewed, and the new clue has been proposed that systematically investigation of the essence of different folding mechanism between the two types of protein would help to provide useful insight for more efficient protein rotational design.

Key words: Protein de novo design, Protein folding, Target structure, Kinetic features of folding

张竹青. 全新设计蛋白质的折叠机制[J]. 物理化学学报, 2012, 28(10), 2381-2389. doi: 10.3866/PKU.WHXB201209144

ZHANG Zhu-Qing. Folding Mechanism of De novo Designed Proteins[J]. Acta Phys. -Chim. Sin. 2012, 28(10), 2381-2389. doi: 10.3866/PKU.WHXB201209144

链接本文: https://www.whxb.pku.edu.cn/CN/10.3866/PKU.WHXB201209144

https://www.whxb.pku.edu.cn/CN/Y2012/V28/I10/2381

参考文献

(1) Anfinsen, C. B.; Haber, E.; Sela, M.; White, F. H., Jr. Proc. Natl. Acad. Sci. U. S. A. 1961, 47, 1309. doi: 10.1073/pnas.47.9.1309
(2) Anfinsen, C. B. Science 1973, 181, 223. doi: 10.1126/science.181.4096.223
(3) Berman, H. M.;Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.;Weissig, H.; Shindyalov, I. N.; Bourne, P. E. Nucleic Acids Res. 2000, 28, 235. doi: 10.1093/nar/28.1.235
(4) Uversky, V. N. Protein Sci. 2002, 11, 739. doi: 10.1110/ps.4210102
(5) Huang, Y. Q.; Liu, Z. R. Acta Phys. -Chim. Sin. 2010, 26, 2061.[黄永棋, 刘志荣. 物理化学学报, 2010, 26, 2061.]
(6) Moult, J.; Pedersen, J. T.; Judson, R.; Fidelis, K. Proteins 1995,23, R2.
(7) Minton, A. P. Curr. Opin. Struct. Biol. 2000, 10, 34. doi: 10.1016/S0959-440X(99)00045-7
(8) Jackson, S. E.; Fersht, A. R. Biochemistry 1991, 30, 10428. doi: 10.1021/bi00107a010
(9) Leopold, P. E.; Montal, M.; Onuchic, J. N. Proc. Natl. Acad. Sci. U. S. A. 1992, 89, 8721. doi: 10.1073/pnas.89.18.8721
(10) Dill, K. A.; Chan, H. S. Nat. Struct. Biol. 1997, 4, 10. doi: 10.1038/nsb0197-10
(11) Duan, Y.; Kollman, P. A. Science 1998, 282, 740. doi: 10.1126/science.282.5389.740
(12) Shaw, D. E.; Maragakis, P.; Lindorff-Larsen, K.; Piana, S.; Dror,R. O.; Eastwood, M. P.; Bank, J. A.; Jumper, J. M.; Salmon, J.K.; Shan, Y.;Wriggers,W. Science 2010, 330, 341. doi: 10.1126/science.1187409
(13) Lindorff-Larse, K.; Piana, S.; Dror, R. O.; Shaw, D. E. Science2011, 334, 517. doi: 10.1126/science.1208351
(14) Shortle, D.; Dimaio, D.; Nathans, D. Annu. Rev. Genet. 1981,15, 265. doi: 10.1146/annurev.ge.15.120181.001405
(15) Leatherbarrow, R. J.; Fersht, A. R. Protein Eng. 1986, 1, 7. doi: 10.1093/protein/1.1.7
(16) Ho, S. P.; DeGrado,W. F. J. Am. Chem. Soc. 1987, 109, 6751.doi: 10.1021/ja00256a032
(17) Ramirez-Alvarado, M.; Blanco, F. J.; Serrano, L. Nat. Struct. Biol. 1996, 3, 604. doi: 10.1038/nsb0796-604
(18) Floudas, C. A. Biotechnol. Bioeng. 2007, 97, 207. doi: 10.1002/bit.21411
(19) Zhang, Y. Curr. Opin. Struct. Biol. 2008, 18, 342. doi: 10.1016/j.sbi.2008.02.004
(20) Floudas, C. A.; Fung, H. K.; McAllister, S. R.; Monnigmann,M.; Rajgaria, R. Chem. Eng. Sci. 2006, 61, 966.
(21) Shakhnovich, E. Chem. Rev. 2006, 106, 1559. doi: 10.1021/cr040425u
(22) Dill, K. A.; Ozkan, S. B.; Shell, M. S.; Thomas, R.W. Annu. Rev. Biophys. 2008, 37, 289. doi: 10.1146/annurev.biophys.37.092707.153558
(23) Thirumalai, D.; O'Brien E. P.; Morrison, G.; Hyeon, C. Annu. Rev. Biophys. 2010, 39, 159. doi: 10.1146/annurev-biophys-051309-103835
(24) Butterfoss, G. L.; Kuhlman, B. Annu. Rev. Biophys. Biomol. Struct. 2006, 35, 49. doi: 10.1146/annurev.biohhys.35.040405.102046
(25) Pantazes, R. J.; Grisewood, M. J.; Maranas, C. D. Curr. Opin. Struct. Biol. 2011, 21, 467. doi: 10.1016/j.sbi.2011.04.005
(26) Lai, L. H. Structure Prediction and Molecular Design of Proteins; Peking University Press: Beijing, 1993. [来鲁华.蛋白质的结构预测与分子设计. 北京: 北京大学出版社,1993.]
(27) Chou, P. Y.; Fasman, G. D. Biochemistry 1974, 13, 222. doi: 10.1021/bi00699a002
(28) Richardson, J. S.; Richardson, D. C. Science 1988, 240, 1648.doi: 10.1126/science.3381086
(29) Kumar, S.; Bansal, M. Proteins 1998, 31, 460. doi: 10.1002/(SICI)1097-0134(19980601)31:4<460::AID-PROT12>3.0.CO;2-D
(30) Goliaei, B.; Minuchehr, Z. FEBS Lett. 2003, 537, 121. doi: 10.1016/S0014-5793(03)00105-4
(31) Fonseca, N. A.; Camacho, R.; Magalhaes, A. L. Proteins 2008,70, 188.
(32) Qi, Y. F.; Liang, H. H.; Han, X. F.; Lai, L. L. Protein Pept. Lett.2012, 19, 345. doi: 10.2174/092986612799363118
(33) Ho, S. P.; DeGrado,W. F. J. Am. Chem. Soc. 1987, 109, 6751.doi: 10.1021/ja00256a032
(34) Hecht, M. H.; Richardson, J. S.; Richardson, D. C.; Ogden, R.C. Science 1990, 249, 884. doi: 10.1126/science.2392678
(35) Fezoui, Y.;Weaver, D. L.; Osterhout, J. J. Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 3675. doi: 10.1073/pnas.91.9.3675
(36) Bryson, J.W.; Desjarlais, J. R.; Handel, T. M.; DeGrado,W. F.Protein Sci. 1998, 7, 1404. doi: 10.1002/pro.5560070617
(37) Moser, R.; Thomas, R. M.; Gutte, B. FEBS Lett. 1983, 157,247. doi: 10.1016/0014-5793(83)80555-9
(38) Blanco, F. J.; Jimenez, M. A.; Herranz, J.; Rico, M.; Santoro, J.;Nieto, J. L. J. Am. Chem. Soc. 1993, 115, 5887. doi: 10.1021/ja00066a092
(39) Blanco, F. J.; Rivas, G.; Serrano, L. Nat. Struct. Biol. 1994, 1,584. doi: 10.1038/nsb0994-584
(40) Ramirez-Alvarado, M.; Blanco, F. J.; Serrano, L. Nat. Struct. Biol. 1996, 3, 604. doi: 10.1038/nsb0796-604
(41) Kortemme, T.; Ramirez-Alvarado, M.; Serrano, L. Science1998, 281, 253. doi: 10.1126/science.281.5374.253
(42) Carulla, N.;Woodward, C.; Barany, G. Protein. Sci. 2002, 11,1539. doi: 10.1110/ps.4440102
(43) Dahiyat, B. I.; Mayo, S. L. Science 1997, 278, 82. doi: 10.1126/science.278.5335.82
(44) Riddle, D. S.; Santiago, J. V.; Bray-Hall, S. T.; Doshi, N.;Grantcharova, V. P.; Yi, Q.; Baker, D. Nat. Struct. Biol. 1997, 4,805. doi: 10.1038/nsb1097-805
(45) Kim, D. E.; Gu, H.; Baker, D. Proc. Natl. Acad. Sci. U. S. A.1998, 95, 4982. doi: 10.1073/pnas.95.9.4982
(46) Dantas, G.; Kuhlman, B.; Callender, D.;Wong, M.; Baker, D.J. Mol. Biol. 2003, 332, 449. doi: 10.1016/S0022-2836(03)00888-X
(47) Kuhlman, B.; Dantas, G.; Ireton, G. C.; Varani, G.; Stoddard, B.L.; Baker, D. Science 2003, 302, 1364. doi: 10.1126/science.1089427
(48) Liang, H.; Chen, H.; Fan, K.;Wei, P.; Guo, X.; Jin, C.; Zeng, C.;Tang, C.; Lai, L. Angew. Chem. Int. Edit. 2009, 48, 3301. doi: 10.1002/anie.200805476
(49) Zhu, C.; Zhang, C.; Liang, H.; Lai, L. Protein & Cell 2011, 2,1006. doi: 10.1007/s13238-011-1121-3
(50) Samish, I.; MacDermaid, M.; Perez-Aguilar, J. M.; Saven, J. G.Annu. Rev. Phys. Chem. 2011, 62, 129. doi: 10.1146/annurevphyschem-032210-103509
(51) Li, H.; Helling, R.; Tang, C.;Wingreen, N. Science 1996, 273,666. doi: 10.1126/science.273.5275.666
(52) Saven, J. G. Chem. Rev. 2011, 101, 3113.
(53) Hellinga, H.W. Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 10015.doi: 10.1073/pnas.94.19.10015
(54) Zhang, C. S.; Lai, L. H. Biochem. Soc. Trans. 2011, 39, 1382.doi: 10.1042/BST0391382
(55) Zhang, C. S.; Lai, L. H. Proteins 2012, 80, 1078. doi: 10.1002/prot.24009
(56) Robertson, D. E.; Farid, R. S.; Moser, C. C.; Urbauer, J. L.;Mulholland, S. E.; Pidikiti, R.; Lear, J. D.;Wand, A. J.;DeGrado,W. F.; Dutton, P. L. Nature 1994, 368, 425. doi: 10.1038/368425a0
(57) Reynolds, K. A.; Hanes, M. S.; Thomson, J. M.; Antczak, A. J.;Berger, J. M.; Bonomo, R. A.; Kirsch, J. F.; Handel, T. M.J. Mol. Biol. 2008, 382, 1265. doi: 10.1016/j.jmb.2008.05.051
(58) Liu, S.; Zhu, X.; Liang, H.; Cao, A.; Chang, Z.; Lai, L. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 5330. doi: 10.1073/pnas.0606198104
(59) Bai, H. J.; Lai, L. H. Acta Phys. -Chim. Sin. 2010, 26, 1988.[白红军, 来鲁华. 物理化学学报, 2010, 26, 1988.] doi: 10.3866/PKU.WHXB20100725
(60) Jiang, L.; Althoff, E. A.; Clemente, F. R.; Doyle, L.;Rothlisberger, D.; Zanghellini, A.; Gallaher, J. L.; Betker, J. L.;Tanaka, F.; Barbas, C. F., III; Hilvert, D.; Houk, K. N.;Stoddard, B. L.; Baker, D. Science 2008, 319, 1387. doi: 10.1126/science.1152692
(61) Stefani, M.; Dobson, C. M. J. Mol. Med. 2003, 81, 678. doi: 10.1007/s00109-003-0464-5
(62) Levinthal, C. J. Chem. Phys. 1968, 65, 44.
(63) Viguera, A. R.; Martinez, J. C.; Filimonov, V. V.; Mateo, P. L.;Serrano, L. Biochemistry 1994, 33, 2142. doi: 10.1021/bi00174a022
(64) Otzen, D. E.; Kristensen, O.; Proctor, M.; Oliveberg, M.Biochemistry 1999, 38, 6499. doi: 10.1021/bi982819j
(65) Plaxco, K.W.; Baker, D. Proc. Natl. Acad. Sci. U. S. A. 1998,95, 13591. doi: 10.1073/pnas.95.23.13591
(66) Taverna, D. M.; Goldstein, R. A. Proteins 2002, 46, 105. doi: 10.1002/prot.10016
(67) Matouschek, A.; Kellis, J. T.; Serrano, L.; Fersht, A. R. Nature1989, 340, 122. doi: 10.1038/340122a0
(68) Fersht, A. R.; Matouschek, A.; Serrano, L. J. Mol. Biol. 1992,224, 771. doi: 10.1016/0022-2836(92)90561-W
(69) Scaloni, F.; Federici, L.; Brunori, M.; Gianni, S. Proc. Natl. Acad. Sci. U. S. A. 2010, 95, 4982.
(70) Morris, E. R.; Searle, M. S. Curr. Protoc. Protein. Sci. 2012, 28,Unit 28.2.1.
(71) Gomez-Hens, A.; Perez-Bendito, D. Anal. Chim. Acta 1991,242, 147. doi: 10.1016/0003-2670(91)87060-K
(72) Bai, Y.W.; Sosnick, T. R.; Mayne, L.; Englander, S.W. Science1995, 269, 192. doi: 10.1126/science.7618079
(73) Gai, F.; Du, D.; Xu, Y. Methods. Mol. Biol. 2007, 350, 1.
(74) Borgia, A.;Williams, P. M.; Clarke, J. Annu. Rev. Biochem.2008, 77, 101. doi: 10.1146/annurev.biochem.77.060706.093102
(75) Chung, H. S.; McHale, K.; Louis, J. M.; Eaton,W. A. Science2012, 335, 981. doi: 10.1126/science.1215768
(76) Onuchic, J. N.; Luthey-Schulten, Z.;Wolynes, P. G. Annu. Rev. Phys. Chem. 1997, 48, 545. doi: 10.1146/annurev.physchem.48.1.545
(77) Gsponer, J.; Vendruscolo, M. Protein Pept. Lett. 2006, 13, 287.doi: 10.2174/092986606775338407
(78) Dill, K. A. Biochemistry 1985, 24, 1501. doi: 10.1021/bi00327a032
(79) Clementi, C. Curr. Opin. Struct. Biol. 2008, 18, 10. doi: 10.1016/j.sbi.2007.10.005
(80) Ueeda, Y.; Taketomi, H.; Gō, N. Biopolymers 1978, 17, 1531.doi: 10.1002/bip.1978.360170612
(81) Plaxco, K.W.; Simons, K. T.; Baker, D. J. Mol. Biol. 1998, 277,985. doi: 10.1006/jmbi.1998.1645
(82) Clementi, C.; Nymeyer, H.; Onuchic, J. N. J. Mol. Biol. 2000,298, 937. doi: 10.1006/jmbi.2000.3693
(83) Hills, R. D., Jr.; Brooks, C. L., III. Int. J. Mol. Sci. 2009, 10,889. doi: 10.3390/ijms10030889
(84) Chan, H. S.; Zhang, Z.;Wallin, S.; Liu, Z. Annu. Rev. Phys. Chem. 2011, 62, 301. doi: 10.1146/annurev-physchem-032210-103405
(85) Cho, S. S.; Levy, Y.;Wolynes, P. G. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 434. doi: 10.1073/pnas.0810218105
(86) Cho, S. S.;Weinkam, P.;Wolynes, P. G. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 118. doi: 10.1073/pnas.0709376104
(87) Zuo, G.;Wang, J.;Wang,W. Proteins 2006, 63, 165. doi: 10.1002/prot.20857
(88) Badasyan, A.; Liu, Z.; Chan, H. S. J. Mol. Biol. 2008, 384, 512.doi: 10.1016/j.jmb.2008.09.023
(89) Liu, Z.; Chan, H. S. J. Mol. Biol. 2005, 349, 872. doi: 10.1016/j.jmb.2005.03.084
(90) Ferguson, A.; Liu, Z.; Chan, H. S. J. Mol. Biol. 2009, 389, 619.doi: 10.1016/j.jmb.2009.04.011
(91) Zarrine-Afsar, A.;Wallin, S.; Neculai, A. M.; Neudecker, P.;Howell, P. L.; Davidson, A. R.; Chan, H. S. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 9999. doi: 10.1073/pnas.0801874105
(92) Zarrine-Afsar, A.; Zhang, Z.; Schweiker, K. L.; Makhatadze, G.I.; Davidson, A. R.; Chan, H. S. Proteins 2012, 80, 858. doi: 10.1002/prot.23243
(93) Su, J. G.; Chen,W. Z.;Wang, C. X. Proteins 2010, 78, 2157.
(94) Azia, A.; Levy, Y. J. Mol. Biol. 2009, 393, 527. doi: 10.1016/j.jmb.2009.08.010
(95) Liu, Z.; Reddy, G.; O'Brien, E. P.; Thirumalai, D. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 7787. doi: 10.1073/pnas.1019500108
(96) Liu, Z.; Reddy, G.; Thirumalai, D. J. Phys. Chem. B 2012, 116,6707. doi: 10.1021/jp211941b
(97) Wu, L.; Li,W.; Liu, F.; Zhang, J.;Wang, J.;Wang,W. J. Chem. Phys. 2009, 131, 065105. doi: 10.1063/1.3200952
(98) Wu, L.; Zhang, J.;Wang, J.; Li,W. F.;Wang,W. Phys. Rev. E2007, 75, 031914. doi: 10.1103/PhysRevE.75.031914
(99) Wu, L.; Zhang, J.; Qin, M.; Liu, F.;Wang,W. J. Chem. Phys.2008, 128, 235103. doi: 10.1063/1.2943202
(100) McCammon, J. A.; Gelin, B. R.; Karplus, M. Nature 1977,267, 585. doi: 10.1038/267585a0
(101) Zhu, Y.; Alonso, D. O.; Maki, K.; Huang, C. Y.; Lahr, S. J.;Daggett, V.; Roder, H.; DeGrado,W. F.; Gai, F. Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 15486. doi: 10.1073/pnas.2136623100
(102) Zhu, Y.; Fu, X.;Wang, T.; Tamura, A.; Takada, S.; Saven, J. G.;Gai, F. Chem. Phys. 2004, 307, 99. doi: 10.1016/j.chemphys.2004.05.008
(103) Wang, T.; Zhu, Y.; Gai, F. J. Phys. Chem. B 2004, 108, 3694.doi: 10.1021/jp049652q
(104) Gillespie, B.; Vu, D. M.; Shah, P. S.; Marshall, S. A.; Dyer, R.B.; Mayo, S. L.; Plaxco, K.W. J. Mol. Biol. 2003, 330, 813.doi: 10.1016/S0022-2836(03)00616-8
(105) Scalley-Kim, M.; Baker, D. J. Mol. Biol. 2004, 338, 573. doi: 10.1016/j.jmb.2004.02.055
(106) Sadqi, M.; de Alba, E.; Perez-Jimenez, R.; Sanchez-Ruiz, J.M.; Muñoz, V. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 4127.doi: 10.1073/pnas.0812108106
(107) Watters, A. L.; Deka, P.; Corrent, C.; Callender, D.; Varani, G.;Sosnick, T.; Baker, D. Cell 2007, 128, 613. doi: 10.1016/j.cell.2006.12.042
(108) Zhang, Z.; Chan, H. S. Biophys. J. 2009, 96, L25.
(109) Zhang, Z.; Chan, H. S. Proc. Natl. Acad. Sci. U. S. A. 2010,107, 2920. doi: 10.1073/pnas.0911844107
(110) Qi, Y.; Huang, Y.; Liang, H.; Liu, Z.; Lai, L. Biophys. J. 2010,98, 321. doi: 10.1016/j.bpj.2009.10.018

[1]	曹傲能. 蛋白质结构的“限域下最低能量结构片段”假说与蛋白质进化的“石器时代”[J]. 物理化学学报, 2020, 36(1): 1907002 - .
[2]	李咏, 周玮, 代志军, 陈渊, 王志明, 袁哲明. 基于序列特征筛选与支持向量回归预测蛋白质折叠速率[J]. 物理化学学报, 2014, 30(6): 1091 -1098 .
[3]	支泽勇, 刘鹏程, 黄岩谊, 赵新生. 用于单分子动力学实验的微流控混合器[J]. 物理化学学报, 2011, 27(08): 1990 -1995 .
[4]	黄永棋, 刘志荣. 天然无序蛋白质: 序列-结构-功能的新关系[J]. 物理化学学报, 2010, 26(08): 2061 -2072 .
[5]	高萌, 姚新秋, 佘振苏, 刘志荣, 朱怀球. 蛋白折叠中的暂态结构与表面水分子慢尺度动力学[J]. 物理化学学报, 2010, 26(07): 1998 -2006 .
[6]	刘岳, 李晓琴, 徐海松, 乔辉. 蛋白质折叠类型的分类建模与识别[J]. 物理化学学报, 2009, 25(12): 2558 -2564 .
[7]	王铮, 赖兵, 曹洁, 李竹, 瞿丽丽, 曹傲能, 来鲁华. 小分子热休克蛋白Mj HSP16.5的分级变性[J]. 物理化学学报, 2008, 24(10): 1745 -1750 .
[8]	沙印林;黄永亮. 蛋白质全新设计：八残基序列形成发夹结构的圆二色谱[J]. 物理化学学报, 2002, 18(06): 504 -507 .