Fink A L
Department of Chemistry and Biochemistry, The University of California, Santa Cruz, California, USA.
Physiol Rev. 1999 Apr;79(2):425-49. doi: 10.1152/physrev.1999.79.2.425.
The folding of most newly synthesized proteins in the cell requires the interaction of a variety of protein cofactors known as molecular chaperones. These molecules recognize and bind to nascent polypeptide chains and partially folded intermediates of proteins, preventing their aggregation and misfolding. There are several families of chaperones; those most involved in protein folding are the 40-kDa heat shock protein (HSP40; DnaJ), 60-kDa heat shock protein (HSP60; GroEL), and 70-kDa heat shock protein (HSP70; DnaK) families. The availability of high-resolution structures has facilitated a more detailed understanding of the complex chaperone machinery and mechanisms, including the ATP-dependent reaction cycles of the GroEL and HSP70 chaperones. For both of these chaperones, the binding of ATP triggers a critical conformational change leading to release of the bound substrate protein. Whereas the main role of the HSP70/HSP40 chaperone system is to minimize aggregation of newly synthesized proteins, the HSP60 chaperones also facilitate the actual folding process by providing a secluded environment for individual folding molecules and may also promote the unfolding and refolding of misfolded intermediates.
细胞中大多数新合成蛋白质的折叠需要多种被称为分子伴侣的蛋白质辅助因子的相互作用。这些分子识别并结合新生的多肽链以及蛋白质部分折叠的中间体，防止它们聚集和错误折叠。伴侣蛋白有几个家族；在蛋白质折叠中最主要涉及的是40 kDa热休克蛋白（HSP40；DnaJ）、60 kDa热休克蛋白（HSP60；GroEL）和70 kDa热休克蛋白（HSP70；DnaK）家族。高分辨率结构的可得性有助于更详细地了解复杂的伴侣蛋白机制，包括GroEL和HSP70伴侣蛋白的ATP依赖反应循环。对于这两种伴侣蛋白来说，ATP的结合引发关键的构象变化，导致结合的底物蛋白释放。虽然HSP70/HSP40伴侣蛋白系统的主要作用是使新合成蛋白质的聚集最小化，但HSP60伴侣蛋白还通过为单个折叠分子提供一个隐蔽的环境来促进实际的折叠过程，并且还可能促进错误折叠中间体的解折叠和重新折叠。
