Houry W A
Department of Biochemistry, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Curr Protein Pept Sci. 2001 Sep;2(3):227-44. doi: 10.2174/1389203013381134.
Folding of polypeptides in the cell typically requires the assistance of a set of proteins termed molecular chaperones. Chaperones are an essential group of proteins necessary for cell viability under both normal and stress conditions. There are several chaperone systems which carry out a multitude of functions all aimed towards insuring the proper folding of target proteins. Chaperones can assist in the efficient folding of newly-translated proteins as these proteins are being synthesized on the ribosome and can maintain pre-existing proteins in a stable conformation. Chaperones can also promote the disaggregation of preformed protein aggregates. Many of the identified chaperones are also heat shock proteins. The general mechanism by which chaperones carry out their function usually involves multiple rounds of regulated binding and release of an unstable conformer of target polypeptides. The four main chaperone systems in the Escherichia coli cytoplasm are as follows. (1) Ribosome-associated trigger factor that assists in the folding of newly-synthesized nascent chains. (2) The Hsp 70 system consisting of DnaK (Hsp 70), its cofactor DnaJ (Hsp 40), and the nucleotide exchange factor GrpE. This system recognizes polypeptide chains in an extended conformation. (3) The Hsp 60 system, consisting of GroEL (Hsp 60) and its cofactor GroES (Hsp 10), which assists in the folding of compact folding intermediates that expose hydrophobic surfaces. (4) The Clp ATPases which are typically members of the Hsp 100 family of heat shock proteins. These ATPases can unfold proteins and disaggregate preformed protein aggregates to target them for degradation. Several advances have recently been made in characterizing the structure and function of all of these chaperone systems. These advances have provided us with a better understanding of the protein folding process in the cell.
细胞中多肽的折叠通常需要一组被称为分子伴侣的蛋白质的协助。伴侣蛋白是在正常和应激条件下细胞存活所必需的一类重要蛋白质。有几种伴侣蛋白系统，它们执行多种功能，所有这些功能都旨在确保靶蛋白的正确折叠。伴侣蛋白可以在新翻译的蛋白质在核糖体上合成时协助其有效折叠，并能使已有的蛋白质保持稳定的构象。伴侣蛋白还可以促进预先形成的蛋白质聚集体的解聚。许多已鉴定的伴侣蛋白也是热休克蛋白。伴侣蛋白执行其功能的一般机制通常涉及对靶多肽不稳定构象的多轮调节性结合和释放。大肠杆菌细胞质中的四个主要伴侣蛋白系统如下。（1）与核糖体相关的触发因子，它协助新合成的新生链折叠。（2）由DnaK（Hsp 70）、其辅因子DnaJ（Hsp 40）和核苷酸交换因子GrpE组成的Hsp 70系统。该系统识别处于伸展构象的多肽链。（3）由GroEL（Hsp 60）及其辅因子GroES（Hsp 10）组成的Hsp 60系统，它协助暴露疏水表面的紧密折叠中间体的折叠。（4）Clp ATP酶，它们通常是热休克蛋白Hsp 100家族的成员。这些ATP酶可以使蛋白质解折叠并使预先形成的蛋白质聚集体解聚，以便将它们靶向降解。最近在表征所有这些伴侣蛋白系统的结构和功能方面取得了一些进展。这些进展使我们对细胞中的蛋白质折叠过程有了更好的理解。
