Ranson N A, Farr G W, Roseman A M, Gowen B, Fenton W A, Horwich A L, Saibil H R
Department of Crystallography, Birkbeck College London, Malet Street, London WC1E 7HX, United Kingdom.
Cell. 2001 Dec 28;107(7):869-79. doi: 10.1016/s0092-8674(01)00617-1.
The chaperonin GroEL drives its protein-folding cycle by cooperatively binding ATP to one of its two rings, priming that ring to become folding-active upon GroES binding, while simultaneously discharging the previous folding chamber from the opposite ring. The GroEL-ATP structure, determined by cryo-EM and atomic structure fitting, shows that the intermediate domains rotate downward, switching their intersubunit salt bridge contacts from substrate binding to ATP binding domains. These observations, together with the effects of ATP binding to a GroEL-GroES-ADP complex, suggest structural models for the ATP-induced reduction in affinity for polypeptide and for cooperativity. The model for cooperativity, based on switching of intersubunit salt bridge interactions around the GroEL ring, may provide general insight into cooperativity in other ring complexes and molecular machines.
伴侣蛋白GroEL通过将ATP协同结合到其两个环之一上来驱动其蛋白质折叠循环，使该环在结合GroES时准备好变得具有折叠活性，同时从相对的环中排出先前的折叠腔室。通过冷冻电镜和原子结构拟合确定的GroEL-ATP结构表明，中间结构域向下旋转，将它们的亚基间盐桥接触从底物结合结构域切换到ATP结合结构域。这些观察结果，连同ATP与GroEL-GroES-ADP复合物结合的影响，提出了ATP诱导的对多肽亲和力降低和协同作用的结构模型。基于GroEL环周围亚基间盐桥相互作用切换的协同作用模型，可能为深入了解其他环复合物和分子机器中的协同作用提供一般性的见解。
