Folding and binding cascades: Dynamic landscapes and population shifts
Folding and binding cascades: Dynamic landscapes and population shifts
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DOI：
10.1110/ps.9.1.10
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发表时间：
2008-12
期刊：
影响因子：
8
通讯作者：
Sandeep Kumar;B. Ma;Chung-Jung Tsai;N. Sinha;R. Nussinov
中科院分区：
文献类型：
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作者：
Sandeep Kumar;B. Ma;Chung-Jung Tsai;N. Sinha;R. Nussinov
鉴于先前我们已经成功地利用折叠漏斗概念来使结合机制合理化（Ma B，Kumar S，Tsai CJ，Nussinov R，1999，Protein Eng 12：713-720）并描述结合（Tsai CJ，Kumar S，Ma B，Nussinov R，1999，Protein Sci 8：1181-1190），在此我们进一步扩展折叠漏斗的概念，说明其在解释酶途径、多分子缔合和变构中的效用。该延伸基于这样的认识：漏斗不是静止的;相反，它们是动态的，取决于物理或结合条件（Tsai CJ，Ma B，Nussinov R，1999，Proc Natl Acad Sci USA 96：9970-9972）。不同的结合状态改变了蛋白质的周围环境。环境的变化反过来又表现为能量景观的变化，具有不同的形状和构象异构体的分布。因此，蛋白质的功能及其性质不仅取决于静态折叠的三维结构;它们还取决于其构象亚态的分布，特别是不同环境下群体的重新分布。也就是说，蛋白质的功能来源于其动态能量景观，由其周围环境的变化引起。
Whereas previously we have successfully utilized the folding funnels concept to rationalize binding mechanisms (Ma B, Kumar S, Tsai CJ, Nussinov R, 1999, Protein Eng 12:713–720) and to describe binding (Tsai CJ, Kumar S, Ma B, Nussinov R, 1999, Protein Sci 8:1181–1190), here we further extend the concept of folding funnels, illustrating its utility in explaining enzyme pathways, multimolecular associations, and allostery. This extension is based on the recognition that funnels are not stationary; rather, they are dynamic, depending on the physical or binding conditions (Tsai CJ, Ma B, Nussinov R, 1999, Proc Natl Acad Sci USA 96:9970–9972). Different binding states change the surrounding environment of proteins. The changed environment is in turn expressed in shifted energy landscapes, with different shapes and distributions of populations of conformers. Hence, the function of a protein and its properties are not only decided by the static folded three‐dimensional structure; they are determined by the distribution of its conformational substates, and in particular, by the redistributions of the populations under different environments. That is, protein function derives from its dynamic energy landscape, caused by changes in its surroundings.