通过调节共伴侣蛋白 GroES 来刺激单个环 GroEL 变体的底物折叠活性。
Stimulating the substrate folding activity of a single ring GroEL variant by modulating the cochaperonin GroES.
机构信息
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47405.
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47405.
出版信息
J Biol Chem. 2011 Sep 2;286(35):30401-30408. doi: 10.1074/jbc.M111.255935. Epub 2011 Jul 10.
In mediating protein folding, chaperonin GroEL and cochaperonin GroES form an enclosed chamber for substrate proteins in an ATP-dependent manner. The essential role of the double ring assembly of GroEL is demonstrated by the functional deficiency of the single ring GroEL(SR). The GroEL(SR)-GroES is highly stable with minimal ATPase activity. To restore the ATP cycle and the turnover of the folding chamber, we sought to weaken the GroEL(SR)-GroES interaction systematically by concatenating seven copies of groES to generate groES(7). GroES Ile-25, Val-26, and Leu-27, residues on the GroEL-GroES interface, were substituted with Asp on different groES modules of groES(7). GroES(7) variants activate ATP activity of GroEL(SR), but only some restore the substrate folding function of GroEL(SR), indicating a direct role of GroES in facilitating substrate folding through its dynamics with GroEL. Active GroEL(SR)-GroES(7) systems may resemble mammalian mitochondrial chaperonin systems.
在介导蛋白质折叠过程中，伴侣蛋白 GroEL 和共伴侣蛋白 GroES 以 ATP 依赖的方式形成一个封闭的腔室来容纳底物蛋白。GroEL 双环组装的重要作用是由单环 GroEL（SR）的功能缺陷证明的。GroEL（SR）-GroES 具有高度稳定性和最小的 ATPase 活性。为了恢复 ATP 循环和折叠腔室的周转率，我们试图通过串联 7 个 groES 拷贝来系统地削弱 GroEL（SR）-GroES 相互作用，从而生成 groES（7）。GroES 上位于 GroEL-GroES 界面上的 Ile-25、Val-26 和 Leu-27 残基被 groES（7）中的不同 groES 模块上的 Asp 取代。GroES（7）变体激活 GroEL（SR）的 ATP 活性，但只有一些能够恢复 GroEL（SR）的底物折叠功能，这表明 GroES 通过与 GroEL 的动态相互作用直接促进底物折叠。活性 GroEL（SR）-GroES（7）系统可能类似于哺乳动物线粒体伴侣蛋白系统。
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