Conformation of peptide fragments of proteins in aqueous solution: implications for initiation of protein folding.
Conformation of peptide fragments of proteins in aqueous solution: implications for initiation of protein folding.
复制标题
水溶液中蛋白质肽片段的构象：对蛋白质折叠起始的影响。
DOI：
10.1021/bi00419a001
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发表时间：
1988
期刊：
影响因子：
2.9
通讯作者：
Lerner,RA
中科院分区：
文献类型：
--
作者：
Wright,PE;Dyson,HJ;Lerner,RA
加利福尼亚州拉霍亚斯克里普斯临床研究所分子生物学系，1988年7月12日收到摘要：灵敏新技术的应用，特别是二维核磁共振波谱的应用，使在天然蛋白质折叠的条件下，能够在水溶液中检测蛋白质短肽片段的折叠结构。这些结构与展开状态处于快速的动态交换中。这些观察为支持蛋白质折叠模型提供了证据，该模型假设折叠结构的局部区域作为折叠过程的起始点。由于这些启动过程预计是快速的，这样的模型与动力学证据是一致的，即蛋白质折叠的速度决定步骤发生在过程的后期，可能涉及错误折叠的中间产物的重排。蛋白质折叠成其天然三维结构的机制仍然是分子生物学中尚未解决的中心问题之一。自从Anfinsen和他的同事的早期实验[在Anfinsen(1973)中回顾]以来，人们已经认识到蛋白质折叠是一个自发的事件，正确折叠所需的所有信息都包含在氨基酸序列中。现有的实验数据表明，许多蛋白质在体外折叠成其天然构象的时间尺度从不到一秒到几分钟不等。显然，折叠不能通过随机搜索所有的连接来发生，对于一个只有100个氨基酸残基的蛋白质来说，这将花费1050年或更长的时间(Levinthal，1968；Wetlafer，1973；Karplus&Weaver，1976)。现在人们普遍认为蛋白质折叠不是通过随机构象搜索发生的，而是通过作为合作生长位点的局部折叠中间体进行的(Anfinsen，1972；Wetlafer，1973；Ptitsyn&Rashin，1975；Richards，1977；Ptitsyn&Finkelstein，1980；Scheraga，1980；Jaenicke，1980；Lesk&Rose，1981；Richardson，1981；Ghelis&Yon，1982；Kim&Baldwin，1982；Karplus&Weaver，
Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, California 92037 Received July 12, 1988 abstract: Applications of sensitive new technologies, in particular, two-dimensional NMR spectroscopy, have allowed detection of folded structures in short peptide fragments of proteins in aqueous solution under conditions where native proteins fold. These structures are in rapid dynamic exchange with unfolded states. These observations provide evidence in support of models for protein folding whichpostulate localized regions of folded structure as initiation sites for the folding process. Since these initiation processes are expected to be rapid, such models are consistent with kinetic evidence that the rate-determining steps of protein folding occur late in the process and probably involve rearrangement of incorrectly folded intermediates. e mechanism by which proteins fold into their native three-dimensional structures remains one of the central un-solved problems of molecular biology. Since the early ex-periments of Anfinsen and co-workers [reviewed in Anfinsen (1973)], it has been recognized that protein folding is a spontaneous event and that all the information required for correct folding is contained within the amino acid sequence. The available experimental data indicate that many proteins fold in vitro into their native conformations on a time scale ranging from less than a second to a few minutes. It is clear that folding cannot occur by a random search of all confor-mations, which, for a protein of only 100 amino acid residues, would take on the order of 1050 years or longer (Levinthal, 1968; Wetlaufer, 1973; Karplus & Weaver, 1976). It is now generally accepted that protein folding does not occur by a random conformational search but proceeds via local folded intermediates that function as sites for cooperative growth (Anfinsen, 1972; Wetlaufer, 1973; Ptitsyn & Rashin, 1975; Richards, 1977; Ptitsyn & Finkelstein, 1980; Scheraga, 1980; Jaenicke, 1980; Lesk & Rose, 1981; Richardson, 1981; Ghelis & Yon, 1982; Kim & Baldwin, 1982; Karplus & Weaver,