The crystal structure of the asymmetric GroEL-GroES-(ADP)(7) chaperonin complex
The crystal structure of the asymmetric GroEL-GroES-(ADP)(7) chaperonin complex
复制标题
DOI：
10.1038/41944
复制
发表时间：
1997-08-21
期刊：
影响因子：
64.8
通讯作者：
Sigler, PB
中科院分区：
文献类型：
--
作者：
Xu, ZH;Horwich, AL;Sigler, PB
伴侣蛋白通过消耗ATP来帮助蛋白质折叠。它们以多亚基蛋白质组装体的形式存在，包括背靠背堆叠的亚基环。在大肠杆菌中，GroEL的不对称中间体由辅伴侣蛋白GroES和仅与七个亚基环之一（顺式环）结合而不与相对环（反式环）结合的核苷酸形成。GroEL-GroES-（ADP）复合物的结构揭示了顺式环的中间结构域和顶端结构域的大的整体移动如何使结合的GroES稳定具有限制于顺式环的ADP的箔室。顶端结构域的升高和扭曲使中央腔体的体积加倍，并将疏水肽结合残基埋在与GroES的界面中以及GroEL亚基之间，留下有利于蛋白质折叠的亲水腔体衬里。顺式赤道结构域的向内倾斜导致反式环中的向外倾斜，其反对第二GroES的结合。当结合新的功能结果，这种负变构机制表明一个模型的ATP驱动的折叠周期，需要一个双环形。
Chaperonins assist protein folding with the consumption of ATP. They exist as multi-subunit protein assemblies comprising rings of subunits stacked back to back. in Escherichia coli, asymmetric Intermediates of GroEL are formed with the co-chaperonin GroES and nucleotides bound only to one of the seven-subunit rings (the cis ring) and not to the opposing ring (the trans ring). The structure of the GroEL-GroES-(ADP), complex reveals how large en bloc movements of the cis ring's intermediate and apical domains enable bound GroES to stabilize a foiling chamber with ADP confined to the cis ring. Elevation and twist of the apical domains double the volume of the central cavity anal bury hydrophobic peptide-binding residues in the interface with GroES, as well as between GroEL subunits, leaving a hydrophilic cavity lining that is conducive to protein folding. An inward tilt of the cis equatorial domain causes an outward tilt in the trans ring that opposes the binding of a second GroES. When combined with new functional results, this negative allosteric mechanism suggests a model for an ATP-driven folding cycle that requires a double toroid.