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Vps4底物结合以及Vps4p底物自抑制募集与释放的偶联机制。

Vps4 substrate binding and coupled mechanisms of Vps4p substrate recruitment and release from autoinhibition.

作者信息

Wienkers H J, Han H, Whitby F G, Hill C P

机构信息

Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA.

出版信息

bioRxiv. 2024 Sep 7:2024.09.07.611824. doi: 10.1101/2024.09.07.611824.

DOI:10.1101/2024.09.07.611824
PMID:39282404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11398535/
Abstract

The ESCRT pathway's AAA+ ATPase, Vps4p, remodels ESCRT-III complexes to drive membrane fission. Here, we use peptide binding assays to further the understanding of substrate specificity and the mechanism of autoinhibition. Our results reveal unexpected sequence preference to the substrate binding groove and an elegant mechanism of regulation that couples localization to substrate with release from autoinhibition.

摘要

ESCRT途径的AAA+ATP酶Vps4p重塑ESCRT-III复合物以驱动膜裂变。在这里，我们使用肽结合试验来进一步了解底物特异性和自抑制机制。我们的结果揭示了底物结合凹槽出人意料的序列偏好，以及一种将定位与底物偶联并从自抑制中释放的精妙调控机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3572/11398535/532237b227e5/nihpp-2024.09.07.611824v1-f0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3572/11398535/608d0e59cef6/nihpp-2024.09.07.611824v1-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3572/11398535/532237b227e5/nihpp-2024.09.07.611824v1-f0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3572/11398535/608d0e59cef6/nihpp-2024.09.07.611824v1-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3572/11398535/532237b227e5/nihpp-2024.09.07.611824v1-f0014.jpg

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本文引用的文献

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Nat Rev Mol Cell Biol. 2020 Jan;21(1):43-58. doi: 10.1038/s41580-019-0183-6. Epub 2019 Nov 21.
2
Structure of Vps4 with circular peptides and implications for translocation of two polypeptide chains by AAA+ ATPases.Vps4 与环状肽的结构及其对 AAA+ ATPases 转运两条多肽链的影响。
Elife. 2019 Jun 11;8:e44071. doi: 10.7554/eLife.44071.
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Structure and mechanism of the ESCRT pathway AAA+ ATPase Vps4.
ESCRT 途径 AAA+ ATP 酶 Vps4 的结构与机制。
Biochem Soc Trans. 2019 Feb 28;47(1):37-45. doi: 10.1042/BST20180260. Epub 2019 Jan 15.
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Inside job: how the ESCRTs release HIV-1 from infected cells.内部作业：ESCRTs 如何将 HIV-1 从受感染的细胞中释放出来。
Biochem Soc Trans. 2018 Oct 19;46(5):1029-1036. doi: 10.1042/BST20180019. Epub 2018 Aug 28.
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Elife. 2017 Nov 22;6:e31324. doi: 10.7554/eLife.31324.
6
Cryo-EM structures of the ATP-bound Vps4 hexamer and its complex with Vta1 at near-atomic resolution.ATP 结合状态下的 Vps4 六聚体及其与 Vta1 复合物的近原子分辨率冷冻电镜结构。
Nat Commun. 2017 Jul 17;8:16064. doi: 10.1038/ncomms16064.
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Mechanism of Vps4 hexamer function revealed by cryo-EM.冷冻电镜揭示 Vps4 六聚体功能的机制。
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