Martin J
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Box G-J2, Providence, RI 02912, USA.
Biochemistry (Mosc). 1998 Apr;63(4):374-81.
The chaperonin system GroEL/GroES assists in the folding of proteins in the bacterial cytosol. Recent applications of biophysical techniques for the structural analysis of GroEL, GroES, and chaperonin-bound protein folding intermediates have provided the basis for understanding the molecular mechanism of GroEL/GroES action. GroEL, a double-ring complex, binds unfolded proteins at its inner ring surface. Protein folding proceeds in the central cavity of GroEL, after dissociation of the polypeptide has been triggered by ATP hydrolysis in GroEL. Premature release of unfolded protein into external solution is prevented by binding of the cofactor GroES on top of the GroEL cylinder, resulting in an enclosed cage. Upon ATP-dependent dissociation of GroES, substrate protein is eventually released from GroEL in a native or native-like conformation. While current in vitro results about the structure, function, and molecular mechanism of GroEL/GroES-assisted protein folding have led to a quite detailed picture of this complex process, the extent to which the GroEL/GroES system actually participates in the folding of newly-synthesized proteins in the cell is less defined and remains a subject for further studies. Ingenious biochemical and genetic approaches will be necessary to show whether our current view of chaperonin action indeed accurately reflects its modus operandi inside a living cell.
伴侣蛋白系统GroEL/GroES协助细菌胞质溶胶中的蛋白质折叠。生物物理技术最近在GroEL、GroES和与伴侣蛋白结合的蛋白质折叠中间体结构分析中的应用，为理解GroEL/GroES作用的分子机制提供了基础。GroEL是一种双环复合物，在其内环表面结合未折叠的蛋白质。在GroEL中ATP水解触发多肽解离后，蛋白质折叠在GroEL的中央腔中进行。辅因子GroES结合在GroEL圆柱体顶部，形成一个封闭的笼子，可防止未折叠的蛋白质过早释放到外部溶液中。在ATP依赖的GroES解离后，底物蛋白最终以天然或类似天然的构象从GroEL中释放出来。虽然目前关于GroEL/GroES辅助蛋白质折叠的结构、功能和分子机制的体外研究结果，已经使我们对这一复杂过程有了相当详细的了解，但GroEL/GroES系统在细胞中实际参与新合成蛋白质折叠的程度尚不清楚，仍是进一步研究的课题。需要巧妙的生化和遗传方法来证明我们目前对伴侣蛋白作用的看法是否确实准确反映了其在活细胞内的作用方式。
