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普遍保守的 GTPase HflX 是一种 RNA 解旋酶,可修复受热损伤的核糖体。

The universally conserved GTPase HflX is an RNA helicase that restores heat-damaged ribosomes.

机构信息

Structural Biology and Bioinformatics Division, Council of Scientific and Industrial Research - Indian Institute of Chemical Biology, Kolkata, India.

Structural Biology and Bioinformatics Division, Council of Scientific and Industrial Research - Indian Institute of Chemical Biology, Kolkata, India

出版信息

J Cell Biol. 2018 Jul 2;217(7):2519-2529. doi: 10.1083/jcb.201711131. Epub 2018 Jun 21.

DOI:10.1083/jcb.201711131
PMID:29930203
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6028529/
Abstract

The ribosome-associated GTPase HflX acts as an antiassociation factor upon binding to the 50S ribosomal subunit during heat stress in Although HflX is recognized as a guanosine triphosphatase, several studies have shown that the N-terminal domain 1 of HflX is capable of hydrolyzing adenosine triphosphate (ATP), but the functional role of its adenosine triphosphatase (ATPase) activity remains unknown. We demonstrate that HflX possesses ATP-dependent RNA helicase activity and is capable of unwinding large subunit ribosomal RNA. A cryo-electron microscopy structure of the 50S-HflX complex in the presence of nonhydrolyzable analogues of ATP and guanosine triphosphate hints at a mode of action for the RNA helicase and suggests the linker helical domain may have a determinant role in RNA unwinding. Heat stress results in inactivation of the ribosome, and we show that HflX can restore heat-damaged ribosomes and improve cell survival.

摘要

核糖体相关 GTP 酶 HflX 在热应激期间与 50S 核糖体亚基结合,充当抗聚集因子。尽管 HflX 被认为是一种鸟苷三磷酸酶,但有几项研究表明 HflX 的 N 端结构域 1 能够水解三磷酸腺苷 (ATP),但其三磷酸腺苷酶 (ATPase) 活性的功能作用尚不清楚。我们证明 HflX 具有依赖于 ATP 的 RNA 解旋酶活性,并能够解旋大亚基核糖体 RNA。在存在非水解型 ATP 和鸟苷三磷酸类似物的情况下,50S-HflX 复合物的冷冻电子显微镜结构提示了 RNA 解旋酶的作用模式,并表明连接螺旋结构域可能在 RNA 解旋中起决定作用。热应激导致核糖体失活,我们表明 HflX 可以恢复受热损伤的核糖体并提高细胞存活率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/ab28d1ab1945/JCB_201711131_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/881e76cf87d6/JCB_201711131_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/e344f546b04a/JCB_201711131_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/33208f774002/JCB_201711131_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/846f542ea684/JCB_201711131_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/0068da35e5f4/JCB_201711131_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/57ad3e841a7b/JCB_201711131_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/ab28d1ab1945/JCB_201711131_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/881e76cf87d6/JCB_201711131_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/e344f546b04a/JCB_201711131_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/33208f774002/JCB_201711131_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/846f542ea684/JCB_201711131_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/0068da35e5f4/JCB_201711131_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/57ad3e841a7b/JCB_201711131_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7cb/6028529/ab28d1ab1945/JCB_201711131_Fig6.jpg

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