物理化学学报 >> 2013, Vol. 29 >> Issue (09): 1842-1850.doi: 10.3866/PKU.WHXB201307011

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模型多肽Trp-Cage折叠形成机制的研究进展

吴晓敏1,2, 袁晓辉3, 薛书蕾1, 查岭生1, 王光利1, 张海军1   

  1. 1 淮北师范大学生命科学学院, 资源植物生物学安徽省重点实验室, 安徽 淮北 235000;
    2 东北林业大学生物资源生态利用国家地方联合工程实验室, 哈尔滨 150040;
    3 暨南大学生物医药研究院, 广州 510632
  • 收稿日期:2013-02-26 修回日期:2013-06-28 发布日期:2013-08-28
  • 通讯作者: 吴晓敏, 张海军 E-mail:dolphin1009@sina.com;theobiochem@sina.cn
  • 基金资助:

    国家自然科学基金(81272377, 31100083);安徽省自然科学基金(1208085QC58);安徽省高校省级自然科学研究项目(KJ2012B163,2012SQRL225)及淮北师范大学引进人才基金(600698)资助

Research Progress of the Trp-Cage Formation and Its Folding Mechanism

WU Xiao-Min1,2, YUAN Xiao-Hui3, XUE Shu-Lei1, ZHA Ling-Sheng1, WANG Guang-Li1, ZHANG Hai-Jun1   

  1. 1 Key Laboratory of Resource and Plant Biology of Anhui Province, College of Life Science, Huaibei Normal University, Huaibei 235000, Anhui Province, P. R. China;
    2 National Local Joint Engineering Laboratory of Bio-resource Ecological Utilization, Northeast Forestry University, Harbin 150040, P. R. China;
    3 Institute of Biomedicine, Jinan University, Guangzhou 510632, P. R. China
  • Received:2013-02-26 Revised:2013-06-28 Published:2013-08-28
  • Contact: WU Xiao-Min, ZHANG Hai-Jun E-mail:dolphin1009@sina.com;theobiochem@sina.cn
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (81272377, 31100083), Natural Science Foundation of Anhui Province, China (1208085QC58), Natural Science Foundation fromEducational Commission of Anhui Province, China (KJ2012B163, 2012SQRL225), and Talented Funds of Huaibei Normal University, China (600698).

摘要:

蛋白质折叠是目前结构生物学领域的核心问题之一, 理解蛋白质结构折叠机制及其与生物功能之间的相互关系一直是生命科学家非常重要的研究内容, 并且该研究受到越来越多不同学科领域研究工作者的高度重视. 蛋白质大多数在数十毫秒、微秒或几秒内完成自我折叠过程, 但其折叠过程中所发生的分子结构精细转变却在纳秒甚至更短时间尺度内完成. 由于其折叠时间分辨率的限制, 目前无论是从常规实验还是理论计算角度对其研究都存在一定的难度. 本文首先概述了蛋白质折叠研究在实验和理论模拟方面存在的一些问题,然后以结构典型且可快速折叠的人工设计多肽Trp-cage为例,主要对其折叠过渡温度、折叠形成模型及其肽链上关键氨基酸残基在折叠过程中的作用三个方面进行了详细讨论, 综述了模型多肽Trp-cage的折叠动力学行为分别在实验和理论模拟方面的研究进展. 最后就如何有效化解蛋白质残基间相互作用网络进而降低其折叠机制的复杂性提出了一些新的建议, 不仅有助于阐明该迷你蛋白Trp-cage快速折叠、稳定形成的驱动力成因, 而且也能为蛋白质折叠机制研究和多肽设计提供有益参考.

关键词: 实验与理论模拟, 折叠机制, 过渡温度, 残基突变, 关键氨基酸

Abstract:

Protein folding is considered one of the most important topics in structural biology. An in-depth understanding of the folding-function relationship is one of the most important subjects for biologists, and is of interest to scientific researchers in other disciplines. The folding of proteins is often completed within the order of milliseconds to seconds, whereas the underlying atomistic details corresponding to structural alterations and intermolecular interactions often occur on the nanosecond or even smaller timescales. Accordingly, the unambiguous description of complicated folding behaviors remains inaccessible to routine experimental and theoretically-calculated resolutions. In this paper, we reviewthe problems that exist in recent experimental and theoretical studies examining the protein folding mechanism. The Trp-cage is a fast-folding mini-protein containing merely 20 amino acid residues, but adopts a well-packed hydrophobic core and tertiary contacts. Herein, we use the Trp-cage as an example and summarize the experimental and theoretical research carried out on the Trp-cage formation and its folding mechanism. The presentation primarily focuses on three aspects: (1) the folding temperature; (2) the folding initiation and proposed folding mechanisms; and (3) the role of key residues and its driving force for the folding of the Trp-cage mini-protein. Finally, we provide some suggestions on how to effectively simplify the complicated interaction networks of the Trp-cage mini-protein and decrease the complexity of the folding mechanism. This helps us to clarify the respective and cooperative contributions of residues involved in the formation of the Trp-cage and its folding dynamics, as well as provide useful insights for folding studies and more efficient rational peptide design.

Key words: Experimental and theoretical simulation, Folding mechanism, Transition temperature, Residue mutation, Key residue

MSC2000: 

  • O641