EVIDENCE FOR A MOLTEN GLOBULE-LIKE TRANSITION-STATE IN PROTEIN-FOLDING FROM DETERMINATION OF ACTIVATION VOLUMES
EVIDENCE FOR A MOLTEN GLOBULE-LIKE TRANSITION-STATE IN PROTEIN-FOLDING FROM DETERMINATION OF ACTIVATION VOLUMES
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DOI：
10.1021/bi00015a001
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发表时间：
1995-04-18
期刊：
影响因子：
2.9
通讯作者：
ROYER, CA
中科院分区：
文献类型：
--
作者：
VIDUGIRIS, GJA;MARKLEY, JL;ROYER, CA
蛋白质折叠问题中最重要但又难以捉摸的一个方面在于过渡态的性质。关于过渡态的结构性质的直接信息可以从折叠和展开过渡的激活体积的确定中获得。目前的压力跃变松弛研究的折叠/展开的葡萄球菌核酸酶显示，体积的蛋白质溶剂系统是在过渡状态下比在折叠或展开状态。此外，折叠的激活体积远大于去折叠的激活体积。这些结果支持一个熔融的球状模型的过渡状态的核酸酶，其中的多肽链是在一个崩溃的，松散的包装，溶剂排除的结构。在这个模型中，疏水性崩溃伴随着去溶剂化是多肽链折叠的限速步骤，而折叠状态的溶剂排除膨胀是蛋白质解折叠的限速步骤。
One of the most important, yet elusive, aspects of the protein folding question lies in the nature of the transition state. Direct information about the structural properties of the transition state can be obtained from determination of the activation volumes for the folding and unfolding transitions. The present pressure-jump relaxation study on the folding/unfolding of staphylococcal nuclease reveals that the volume of the protein-solvent system is larger in the transition state than in either the folded or unfolded states. Moreover, the activation volume of folding is much larger than that of unfolding. These results support a molten globule-like model for the transition state of nuclease in which the polypeptide chain is in a collapsed, loosely packed, solvent-excluded structure. In this model, hydrophobic collapse with concomitant desolvation is the rate-limiting step in the folding of the polypeptide chain, and solvent-excluded expansion of the folded state is the rate-limiting step in protein unfolding.