Coupling between allosteric transitions in GroEL and assisted folding of a substrate protein.
Coupling between allosteric transitions in GroEL and assisted folding of a substrate protein.
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GroEL 中的变构转变与底物蛋白的辅助折叠之间的耦合。
DOI：
10.1073/pnas.0700607104
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发表时间：
2007
影响因子：
11.1
通讯作者：
Brooks,BernardR
中科院分区：
文献类型：
--
作者：
Stan,George;Lorimer,GeorgeH;Thirumalai,D;Brooks,BernardR
Escherichia colichaperonin，GroEL，帮助蛋白质在非允许条件下折叠。在反应循环期间，GroEL响应于底物蛋白（SP）、ATP和辅伴侣蛋白GroES的结合而经历变构转变。使用粗粒度表示的GroEL和GroES结构，我们探索变构转换和折叠的模型SP，阿德诺设计的四螺旋束蛋白质，自发产量低之间的联系。GroEL结合SP的系综的结构比散装错误折叠的结构。结合后，动力学上发生在两个阶段，SP不仅失去了天然的三级接触，但也经历了螺旋内容的减少。在GroEL的多价结合和随后的ATP驱动转变期间，SP经历了力诱导的拉伸。在GroES结合时发生的包封后，SP发现自己处于“亲水性”空腔中，在该空腔中它可以达到折叠构象。令人惊讶的是，我们发现，在扩大GroEL腔的原生状态的产量是相对较小的，即使它仍然在它的两倍的自发折叠时间。因此，与迭代退火机制雅阁，需要SP的多轮结合、部分解折叠和释放以提高折叠SP的产率。
Escherichia colichaperonin, GroEL, helps proteins fold under nonpermissive conditions. During the reaction cycle, GroEL undergoes allosteric transitions in response to binding of a substrate protein (SP), ATP, and the cochaperonin GroES. Using coarse-grained representations of the GroEL and GroES structures, we explore the link between allosteric transitions and the folding of a model SP, ade novo-designed four-helix bundle protein, with low spontaneous yield. The ensemble of GroEL-bound SP is less structured than the bulk misfolded structures. Upon binding, which kinetically occurs in two stages, the SP loses not only native tertiary contacts but also experiences a decrease in helical content. During multivalent binding and the subsequent ATP-driven transition of GroEL the SP undergoes force-induced stretching. Upon encapsulation, which occurs upon GroES binding, the SP finds itself in a “hydrophilic” cavity in which it can reach the folded conformation. Surprisingly, we find that the yield of the native state in the expanded GroEL cavity is relatively small even after it remains in it for twice the spontaneous folding time. Thus, in accord with the iterative annealing mechanism, multiple rounds of binding, partial unfolding, and release of the SP are required to enhance the yield of the folded SP.