线粒体内膜 AAA+ 蛋白酶 YME1 的结构解析揭示其底物处理机制

上传 / 管理员 ·2017-11-12 生物学,生物化学,结构生物学,AAA+ 蛋白酶,底物处理机制

论文标题 / Structure of the mitochondrial inner membrane AAA+ protease YME1 gives insight into substrate processing

作者 / Steven E. Glynn, Gabriel C. Lander, et al.

期刊 / Sciecne

发表时间 / 2017-11-03

数字识别码 / 10.1126/science.aao0464

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【论文摘要】

We present an atomic model of a substrate-bound inner mitochondrial membrane AAA+ quality control protease in yeast, YME1. Our ~3.4-angstrom cryo–electron microscopy structure reveals how the adenosine triphosphatases (ATPases) form a closed spiral staircase encircling an unfolded substrate, directing it toward the flat, symmetric protease ring. Three coexisting nucleotide states allosterically induce distinct positioning of tyrosines in the central channel, resulting in substrate engagement and translocation to the negatively charged proteolytic chamber. This tight coordination by a network of conserved residues defines a sequential, around-the-ring adenosine triphosphate hydrolysis cycle that results in stepwise substrate translocation. A hingelike linker accommodates the large-scale nucleotide-driven motions of the ATPase spiral relative to the planar proteolytic base. The translocation mechanism is likely conserved for other AAA+ ATPases.

 

科研圈

(导读 严冰)固定于酵母线粒体内膜的 AAA+ 蛋白酶 YME1 负责线粒体内蛋白质的质量控制,含有 ATPase 域和蛋白酶域。本文通过冷冻电镜解析出其 ATPase 域的高分辨率结构,发现 ATPase 域呈闭合的非对称螺旋阶梯状,将未折叠的底物环绕其中,中央孔道内保守的酪氨酸残基与底物多肽接触,通过 ATP 水解循环改变酪氨酸位置,从而将底物转运至楼梯底部的环状蛋白酶域中。该转运机制很可能也适用于其他的 AAA+ ATPase。

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