Cooperativity, connectivity, and folding pathways of multidomain proteins
Cooperativity, connectivity, and folding pathways of multidomain proteins
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DOI：
10.1073/pnas.0804512105
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发表时间：
2008-09-16
影响因子：
11.1
通讯作者：
Sasai, Masaki
中科院分区：
文献类型：
--
作者：
Itoh, Kazuhito;Sasai, Masaki
多结构域蛋白在原核和真核蛋白质组中都普遍存在。然而，蛋白质折叠的研究主要集中在蛋白质的单个结构域上，而结构域间相互作用对蛋白质折叠的影响的系统研究相对较少。我们在这里讨论这个问题，通过检查人类γ D-晶体蛋白，孢子外壳蛋白S，和串联阵列的R16和R17域的血影蛋白作为示例蛋白质，通过使用基于结构的折叠模型。计算结果一致地解释了折叠途径和突变扰动的影响的实验数据，支持这样的观点，即两个结构域的连接性和在天然构象中的结构域-结构域相互作用的分布是决定协同折叠的动力学和平衡性质的因素。
Multidomain proteins are ubiquitous in both prokaryotic and eukaryotic proteomes. Study on protein folding, however, has concentrated more on the isolated single domains of proteins, and there have been relatively few systematic studies on the effects of domain-domain interactions on folding. We here discuss this issue by examining human gamma D-crystallin, spore coat protein S, and a tandem array of the R16 and R17 domains of spectrin as example proteins by using a structure-based model of folding. The calculated results consistently explain the experimental data on folding pathways and effects of mutational perturbations, supporting the view that the connectivity of two domains and the distribution of domain-domain interactions in the native conformation are factors to determine kinetic and equilibrium properties of cooperative folding.