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”

引用本文: 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): 190700. doi: 10.3866/PKU.WHXB201907002 shu

Citation: Cao Aoneng. "Confined Lowest Energy Structure Fragments (CLESFs)" Hypothesis for Protein Structure and the "Stone Age" of Protein Prebiotic Evolution[J]. Acta Physico-Chimica Sinica, 2020, 36(1): 190700. doi: 10.3866/PKU.WHXB201907002 shu

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”

曹傲能 ^,

上海大学纳米化学与生物学研究所，上海 200444

作者简介: 曹傲能，1969年出生。1989年在浙江大学获学士学位，1995年在浙江大学获硕士学位，1998年在北京大学获博士学位。现上海大学教授。主要研究方向为蛋白质折叠、人工蛋白质设计、纳米生物医学;

通讯作者: 曹傲能, ancao@shu.edu.cn

基金项目:

国家自然科学基金(31871007, 31571024)及国家重点研发计划(2016YFA0201600)资助项目

摘要: 蛋白质折叠问题被称为第二遗传密码，至今未破译；蛋白质序列的天书仍然是“句读之不知，惑之不解”。在最近工作的基础上，我们提出了蛋白质结构的“限域下最低能量结构片段”假说。这一假说指出，蛋白质中存在一些关键的长程强相互作用位点，这些位点相当于标点符号，将蛋白质序列的天书变成可读的句子(多肽片段)。这些片段的天然结构是在这些强长程相互作用位点限域下的能量最低状态。完整的蛋白质结构由这些“限域下最低能量结构片段”拼合而成，而蛋白质整体结构并不一定是全局性的能量最低状态。在蛋白质折叠过程中，局部片段的天然结构倾向性为强长程相互作用的形成提供主要基于焓效应的驱动力，而天然强长程相互作用的形成为局部片段的天然结构提供主要基于熵效应的稳定性。在蛋白质进化早期，可能存在一个“石器时代”，即依附不同界面(比如岩石)的限域作用而稳定的多肽片段先进化出来，后由这些片段逐步进化(包括拼合)而成蛋白质。

关键词:

English

"Confined Lowest Energy Structure Fragments (CLESFs)" Hypothesis for Protein Structure and the "Stone Age" of Protein Prebiotic Evolution

Cao Aoneng ^,

Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, P. R. China

Corresponding author: Aoneng Cao, Email: ancao@shu.edu.cn; Tel: +86-21-66135277

Received Date: 01 July 2019
Accepted Date: 22 August 2019
Revised Date: 05 August 2019
Available Online: 15 January 2020
Fund Project:

The project was supported by the National Natural Science Foundation of China (31871007, 31571024) and the National Key Research and Development Plan of China (2016YFA0201600)

Abstract: The protein folding problem is regarded as the second genetic code which has yet to be deciphered. To date, Anfinsen's thermodynamic hypothesis, i.e., the native structure of a protein is its most stable state, is the only generally accepted theory for protein folding, although exceptions have been reported. However, this hypothesis is a simple overall statement, with no information regarding where or how a protein is folded. The mechanism underlying protein folding has not yet been elucidated, and it is still not clear how the overall sequence (context) determines the structure of a protein. Based on our recent study, we propose a "Confined Lowest Energy Structure Fragments" (CLESFs) hypothesis. This hypothesis states that proteins are CLESFs joined together by a small number of strong constraints (key long-range interactions). Although the native structure of a protein contains various long-range interactions between amino acids that are far apart in the sequence, only a few strong interactions, such as disulfide bonds, hydrophobic packing, structural ion coordination as in zinc fingers, and hydrogen-bonding networks within beta-sheets, are critical. These key long-range interactions serve as a form of punctuation in the "language" of protein sequence and divide the protein sequence into different "sentences, " i.e., fragments (CLESFs). The local native structures of these CLESFs are the lowest energy structures under the confinements of those key long-range interactions, but the overall protein structure is not necessarily the global minimum as Anfinsen hypothesized. The same fragment may adopt different native structures in different proteins. Each native structure of the same fragment in a different protein is a local minimum for the free fragment and the "global minimum" for the fragment under the specific confinement in the specific protein. Essentially, the native local structures of the CLESFs have an enthalpic advantage (local minimum) which serves as a driving force to form the key long-range interactions; the key long-range interactions stabilize the native local structures with entropy effects by excluding enormous amount of random conformations possible for the fragments. Our CLESFs hypothesis suggests that the protein folding code is not as mysterious as previously thought. Only a few critical long-range interactions have principal influence on the local structures of protein fragments. This is why protein fragments can be grafted onto different proteins, and even more notably, can be grafted onto gold nanoparticles to form a "goldbody". Given that short peptides are generally flexible, and flexible peptides are usually unstable and inactive, it is still a mystery how proteins, i.e., peptides that are long enough to fold into unique structures, evolved in the first place. The CLESFs hypothesis implies that prior to the appearance of the first protein that was long enough to fold into a unique stable structure, there might have been a "Stone Age" during prebiotic protein evolution. At that time, short peptides that could not fold by themselves might have been able to adopt active conformations with a few strong anchors to the surface of "stones", such as rocks, solid particles, or vesicles in the primitive soup, forming CLESFs and gaining an evolutionary advantage against degradation. Later, multiple CLESFs on the same "stone" might have assembled in certain ways to perform more complicated functions, and finally, the first protein might have emerged when individual CLESFs joined together and left the "stone".

Key words:

1. [1]
  Sela, M.; White, F. H.; Anfinsen, C. B. Science 1957, 125, 691. doi: 10.1126/science.125.3250.691
2. [2]
  Kennedy, D.; Norman, C. Science 2005, 309, 75. doi: 10.1126/science.309.5731.75
3. [3]
  Cao, A.; Sha, Y.; Lai, L.; Tang, Y. Protein Peptide Lett. 1998, 5, 53.
4. [4]
  Yan, G. H.; Wang, K.; Shao, Z.; Luo, L.; Song, Z. M.; Chen, J.; Jin, R.; Deng, X.; Wang, H.; Cao, Z.; et al. Proc. Nat. Acad. Sci. U.S.A. 2018, 115, E34. doi: 10.1073/pnas.1713526115
5. [5]
  Ramachandran, G. N.; Ramakrishnan, C.; Sasisekharan, V. J. Mol. Biol. 1963, 7, 95. doi: 10.1016/S0022-2836(63)80023-6
6. [6]
  曹傲能, 来鲁华, 唐有祺.生物化学与生物物理进展, 1998, 25 (3), 197. doi: 10.3321/j.issn:1000-3282.1998.03.002Cao, A.; Lai, L.; Tang, Y. Prog. Biochem. Biophys. 1998, 25 (3), 197. doi: 10.3321/j.issn:1000-3282.1998.03.002
7. [7]
  Chou, P. Y.; Fasman, G. D. Biochemistry 1974, 13, 211. doi: 10.1021/bi00699a001
8. [8]
  Pauling, L.; Corey, R. B.; Branson, H. R. Proc. Nat. Acad. Sci. U.S.A. 1951, 37, 205. doi: 10.1073/pnas.37.4.205
9. [9]
  Pauling, L.; Corey, R. B. Proc. Nat. Acad. Sci. U.S.A. 1951, 37, 251. doi: 10.1073/pnas.37.5.251
10. [10]
  Plaxco, K. W.; Simons, K. T.; Baker, D. J. Mol. Biol. 1998, 277, 985. doi: 10.1006/jmbi.1998.1645
11. [11]
  Landschulz, W. H.; Johnson, P. F.; McKnight, S. L. Science 1988, 240, 1759. doi: 10.1126/science.3289117
12. [12]
  Kauzmann, W. Adv. Protein Chem. 1959, 14, 1. doi: 10.1016/S0065-3233(08)60608-7
13. [13]
  赖兵, 李颖, 曹傲能, 来鲁华.物理化学学报, 2001, 17 (10), 865. doi: 10.3866/PKU.WHXB20011001Lai, B.; Li, Y.; Cao, A.; Lai, L. Acta Phys. -Chim. Sin. 2001, 17 (10), 865. doi: 10.3866/PKU.WHXB20011001
14. [14]
  Laity, J. H.; Lee, B. M.; Wright, P. E. Curr. Opin. Struct. Biol. 2001, 11, 39. doi: 10.1016/S0959-440X(00)00167-6
15. [15]
  Richards, F. M. Proc. Nat. Acad. Sci. U.S.A. 1958, 44, 162. doi: 10.1073/pnas.44.2.162
16. [16]
  Potts, Jr. J. T.; Young, D. M.; Anfinsen, C. B. J. Biol. Chem. 1963, 238, 2593. https://www.ncbi.nlm.nih.gov/pubmed/13985757
17. [17]
  王铮, 赖兵, 曹洁, 李竹, 瞿丽丽, 曹傲能, 来鲁华.物理化学学报, 2008, 24 (10), 1745. doi: 10.1016/S1872-1508(08)60070-4Wang, Z.; Lai, B.; Cao, J.; Li, Z.; Qu, L.; Cao, A.; Lai, L. Acta Phys. -Chim. Sin. 2008, 24 (10), 1745. doi: 10.1016/S1872-1508(08)60070-4
18. [18]
  Wu, H. Chin. J. Physiol. 1931, 5 (4), 321. doi: 10.1016/S0065-3233(08)60330-7
19. [19]
  Epstein, C. J.; Goldberger, R. F.; Anfinsen, C. B. Cold Spring Harbor Symp. Quant. Biol. 1963, 28, 439. doi: 10.1101/SQB.1963.028.01.060
20. [20]
  Anfinsen, C. B. Science 1973, 181, 223. doi: 10.1126/science.181.4096.223
21. [21]
  Levinthal, C. J. Chem. Phys. 1968, 65, 44.
22. [22]
  Cao, A.; Welker, E.; Scheraga, H. Biochemistry 2001, 40, 8536. doi: 10.1021/bi010692j
23. [23]
  Radford, S. E.; Dobson, C. M.; Evans, P. A. Nature 1992, 358, 302. doi: 10.1038/358302a0
24. [24]
  Creighton, T. E. Science 1992, 256, 111. doi: 10.1126/science.1373519
25. [25]
  卜佩璇, 何晨晖, 赵新生.物理化学学报, 2019, 35 (5), 546. doi: 10.3866/PKU.WHXB201806072Bu, P.; He, C.; Zhao, X. Acta Phys. -Chim. Sin. 2019, 35 (5), 546. doi: 10.3866/PKU.WHXB201806072
26. [26]
  Clarke, J.; Cota, E.; Fowler, S. B.; Hamill, S. J. Structure 1999, 7 (9), 1145. doi: 10.1016/S0969-2126(99)80181-6
27. [27]
  Cao, A.; Wang, G.; Lai, L.; Tang, Y. Biochem. Bioph. Res. Co. 2002, 291, 795. doi: 10.1006/bbrc.2002.6526
28. [28]
  Kim, P. S.; Baldwin, R. L. Annu. Rev. Biochem. 1982, 51, 459. doi: 10.1146/annurev.bi.51.070182.002331
29. [29]
  Kim, P. S.; Baldwin, R. L. Annu. Rev. Biochem. 1990, 59, 631. doi: 10.1146/annurev.bi.59.070190.003215
30. [30]
  Ptitsyn, O. B.; Rashin, A. A. Biophys. Chem. 1975, 3, 1. doi: 10.1016/0301-4622(75)80033-0
31. [31]
  Schellman, J. A. Compt. Rend. Lab. Carlsberg. Ser. Chim. 1955, 29, 230.
32. [32]
  Tanford, C. J. Am. Chem. Soc. 1962, 84, 4240. doi: 10.1021/ja00881a009
33. [33]
  Creighton, T. E. Trends Biochem. Sci. 1997, 22, 6. doi: 10.1016/S0968-0004(96)20030-1
34. [34]
  Baldwin, R. L. Trends Biochem. Sci. 1989, 14, 291. doi: 10.1016/0968-0004(89)90067-4
35. [35]
  Daggett, V.; Fersht, A. R. Trends Biochem. Sci. 2003, 28, 18. doi: 10.1016/S0968-0004(02)00012-9
36. [36]
  Thirumalai, D.; Samanta, H. S.; Maity, H.; Reddy, G. Trends Biochem. Sci. 2019, 44, 675. doi: 10.1016/j.tibs.2019.04.003
37. [37]
  Hayer-Hartl, M.; Bracher, A.; Hartl, F. U. Trends Biochem. Sci. 2016, 41, 62. doi: 10.1016/j.tibs.2015.07.009
38. [38]
  Šali, A.; Shakhnovich, E.; Karplus, M. Nature 1994, 369, 248. doi: 10.1038/369248a0
39. [39]
  Zhou, R.; Huang, X.; Margulis, C. J.; Berne, B. J. Science 2004, 305, 1605. doi: 10.1126/science.1101176
40. [40]
  Onuchic, J. N.; Nymeyer, H.; García, A. E.; Chahine, J.; Socci, N. D. Adv. Protein Chem. 2000, 53, 152. doi: 10.1016/S0065-3233(00)53003-4
41. [41]
  Wolynes, P. G. Biochimie 2015, 119, 218. doi: 10.1016/j.biochi.2014.12.007
42. [42]
  Harper, J.W.; Vallee, B. L. Biochemistry 1989, 28, 1875. doi: 10.1021/bi00430a067
43. [43]
  Raines, R. T.; Toscano, M. P.; Nierengarten, D. M.; Ha, J. H.; Auerbach, R. J. Biol. Chem. 1995, 270, 17180. doi: 10.1074/jbc.270.29.17180
44. [44]
  Nicaise, M.; Valerio-Lepiniec, M.; Minard, P.; Desmadril, M. Protein Sci. 2004, 13, 1882. doi: 10.1110/ps.03540504
45. [45]
  Kiss, C.; Fisher, H.; Pesavento, E.; Dai, M.; Valero, R.; Ovecka, M.; Nolan, R.; Phipps, M. L.; Velappan, N.; Chasteen, L.; et al. Nucleic Acids Res. 2006, 34 (19), e132. doi: 10.1093/nar/gkl681
46. [46]
  Skerra, A. J. Mol. Recognit. 2000, 13, 167. doi: 10.1002/1099-1352(200007/08)13:4<167::AID-JMR502>3.0.CO;2-9
47. [47]
  Miburn, P. J.; Scheraga, H. A. J. Protein Chem. 1988, 7, 377. doi: 10.1007/BF01024887
48. [48]
  Mottonen, J.; Strand, A.; Symersky, J.; Sweet, R. M.; Danley, D. E.; Geoghegan, K. F.; Gerard, R. D.; Goldsmith, E. J. Nature 1992, 355, 270. doi: 10.1038/355270a0
49. [49]
  Yu, C.; Niu, X.; Jin, F.; Liu, Z.; Jin, C.; Lai, L. Sci. Rep. 2016, 6, 22298. doi: 10.1038/srep22298
50. [50]
  Tompa, P. Trends Biochem. Sci. 2012, 37, 509. doi: 10.1016/j.tibs.2012.08.004
51. [51]
  Cao, A.; Hu, D.; Lai, L. Protein Sci. 2004, 13, 319. doi: 10.1110/ps.03183404
52. [52]
  曹傲能, 汪蔚学, 宇文泰然, 邓巍, 来鲁华.物理化学学报, 2010, 26 (7), 2015. doi: 10.3866/PKU.WHXB20100708Cao, A.; Wang, W.; Yuwen, T.; Deng, W.; Lai, L. Acta Phys. -Chim. Sin. 2010, 26 (7), 2015. doi: 10.3866/PKU.WHXB20100708
53. [53]
  Cao, A.; Ye, Z.; Cai, Z.; Dong, E.; Yang, X.; Liu, G.; Deng, X.; Wang, Y.; Yang, S. T.; Wang, H.; et al. Angew. Chim. Int. Ed. 2010, 49, 3022. doi: 10.1002/anie.200906883
54. [54]
  Liu, Y.; Cao, A. Meth. Enzymol. 2017, 590, 1. doi: 10.1016/bs.mie.2016.12.001
55. [55]
  Liu, Y.; Song, Z. M.; Deng, X.; Cui, Y.; Yang, Y. F.; Han, K.; Jin. R.; Wang, H.; Liu, Y.; Cao, A. Nanomedicine (Lond.) 2015, 10 (13), 2005. doi: 10.2217/NNM.15.56
56. [56]
  Yang, S. T.; Liu, Y.; Wang, Y. W.; Cao, A. Small 2013, 9, 1635. doi: 10.1002/smll.201201492
57. [57]
  Yang, Y.; Xiang, K.; Yang, Y. X.; Wang, Y. W.; Zhang, X.; Cui, Y.; Wang, H.; Zhu, Q.; Fan, L.; Liu, Y.; et al. Nanoscale 2013, 5, 10345. doi: 10.1039/c3nr02508j
58. [58]
  Cai, Z.; Ye, Z.; Yang, X.; Chang, Y.; Wang, H.; Liu, Y.; Cao, A. Nanoscale 2011, 3, 1974. doi: 10.1039/c0nr00956c
59. [59]
  Yang, X.; Cai, Z.; Ye, Z.; Chen, S.; Yang, Y.; Wang, H.; Cao, A. Nanoscale 2012, 4, 414. doi: 10.1039/c1nr11153a
60. [60]
  Cao, Y.; Cui, Y.; Yang, Y.; Hua, J.; Song, Z. M.; Wang, H.; Liu, Y.; Cao, A. Nano Res. 2018, 11 (5), 2512. doi: 10.1007/s12274-017-1876-9
61. [61]
  Schopf, J. W. Science 1993, 260, 640. doi: 10.1126/science.260.5108.640
62. [62]
  Gesteland, R. F.; Atkins, J. F. The RNA World; Cold Spring Harbour Press, New York, USA, 1993.
63. [63]
  Miller, S. L. Science 1953, 117, 528. doi: 10.1126/science.117.3046.528
64. [64]
  Parker, E. T.; Cleaves, H. J.; Dworkin, J. P.; Glavin, D. P.; Callahan, M.; Aubrey, A.; Lazcano, A.; Bada, J. L. Proc. Nat. Acad. Sci. U.S.A. 2011, 108, 5526. doi: 10.1073/pnas.1019191108

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沈阳化工大学材料科学与工程学院沈阳 110142

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”

作者简介: 曹傲能，1969年出生。1989年在浙江大学获学士学位，1995年在浙江大学获硕士学位，1998年在北京大学获博士学位。现上海大学教授。主要研究方向为蛋白质折叠、人工蛋白质设计、纳米生物医学;

通讯作者: 曹傲能, ancao@shu.edu.cn

English

"Confined Lowest Energy Structure Fragments (CLESFs)" Hypothesis for Protein Structure and the "Stone Age" of Protein Prebiotic Evolution

Corresponding author: Aoneng Cao, Email: ancao@shu.edu.cn; Tel: +86-21-66135277

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

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”

作者简介: 曹傲能，1969年出生。1989年在浙江大学获学士学位，1995年在浙江大学获硕士学位，1998年在北京大学获博士学位。现上海大学教授。主要研究方向为蛋白质折叠、人工蛋白质设计、纳米生物医学;

通讯作者: 曹傲能, ancao@shu.edu.cn

English

"Confined Lowest Energy Structure Fragments (CLESFs)" Hypothesis for Protein Structure and the "Stone Age" of Protein Prebiotic Evolution

Corresponding author: Aoneng Cao, Email: ancao@shu.edu.cn; Tel: +86-21-66135277

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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