Xu Z, Horwich A L, Sigler P B
The Howard Hughes Medical Institute, The Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06510, USA.
Nature. 1997 Aug 21;388(6644):741-50. doi: 10.1038/41944.
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)7 complex reveals how large en bloc movements of the cis ring's intermediate and apical domains enable bound GroES to stabilize a folding chamber with ADP confined to the cis ring. Elevation and twist of the apical domains double the volume of the central cavity and 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.
伴侣蛋白通过消耗ATP协助蛋白质折叠。它们以多亚基蛋白质组装体的形式存在，由背靠背堆叠的亚基环组成。在大肠杆菌中，GroEL的不对称中间体与共伴侣蛋白GroES形成，核苷酸仅与七个亚基环之一（顺式环）结合，而不与相对的环（反式环）结合。GroEL-GroES-(ADP)7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规模整体运动如何使结合的GroES稳定一个折叠腔，其中ADP局限于顺式环。顶端结构域的升高和扭转使中央腔的体积加倍，并将疏水肽结合残基埋入与GroES以及GroEL亚基之间的界面中，留下有利于蛋白质折叠的亲水性腔衬里。顺式赤道结构域的向内倾斜导致反式环向外倾斜，从而阻止第二个GroES的结合。当与新的功能结果相结合时，这种负变构机制提出了一种需要双环的ATP驱动折叠循环模型。
