Identifying protein folding cores from the evolution of flexible regions during unfolding
Identifying protein folding cores from the evolution of flexible regions during unfolding
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DOI：
10.1016/s1093-3263(02)00146-8
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发表时间：
2002-12-01
影响因子：
2.9
通讯作者：
Kuhn, LA
中科院分区：
文献类型：
--
作者：
Hespenheide, BM;Rader, AJ;Kuhn, LA
蛋白质的展开可以被描述为从主要刚性的折叠结构到变性状态整体的转变。在展开过程中，氢键和盐桥断裂，使二级和三级结构不稳定。我们之前的工作表明，共价键、盐桥、氢键和疏水相互作用的网络形成了限制，定义了天然蛋白质的哪些区域是柔性的或刚性的（结构稳定）。在这里，我们测试了这样的假设：有关折叠途径的信息被编码在天然状态结构中非共价相互作用的能量层次中。通过稀释盐桥和氢键网络，将它们从最弱到最强逐一破坏，模拟蛋白质结构的增量热变性。在每个步骤中都会识别结构稳定和柔性区域，提供有关变性过程中柔性区域演化的信息。折叠核心或折叠过程中结构形成的中心被预测为由两个或多个具有最大抗变性稳定性的二级结构形成的区域。对于具有不同结构的 10 种蛋白质，我们表明，这种灵活性/稳定性分析预测的折叠核心与天然态氢-氘交换实验确定的折叠核心非常一致。 (C) 2002 Elsevier Science Inc. 保留所有权利。
The unfolding of a protein can be described as a transition from a predominantly rigid, folded structure to an ensemble of denatured states. During unfolding, the hydrogen bonds and salt bridges break, destabilizing the secondary and tertiary structure. Our previous work shows that the network of covalent bonds, salt bridges, hydrogen bonds, and hydrophobic interactions forms constraints that define which regions of the native protein are flexible or rigid (structurally stable). Here, we test the hypothesis that information about the folding pathway is encoded in the energetic hierarchy of non-covalent interactions in the native-state structure. The incremental thermal denaturation of protein structures is simulated by diluting the network of salt bridges and hydrogen bonds, breaking them one by one, from weakest to strongest. The structurally stable and flexible regions are identified at each step, providing information about the evolution of flexible regions during denaturation. The folding core, or center of structure formation during folding, is predicted as the region formed by two or more secondary structures having the greatest stability against denaturation. For 10 proteins with different architectures, we show that the predicted folding cores from this flexibility/stability analysis are in good agreement with those identified by native-state hydrogen-deuterium exchange experiments. (C) 2002 Elsevier Science Inc. All rights reserved.