ATP plays a structural role in Hsp90 function

Michael Reidy

doi:10.1038/s41467-025-61962-0

2025-07-21

Michael Reidy *

Daniel C. Masison

DOI：10.1038/s41467-025-61962-0

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摘要

En 中文

Hsp90是一种高度保守的ATP依赖性分子伴侣，能够围绕客户蛋白形成钳状结构。ATP在Hsp90功能中的作用尚不明确，因为细胞活力需要ATP结合，但不需要水解。本研究提出了支持我们假说的发现，即ATP结合后，γ磷酸基团以受控方式重新定位，与保守精氨酸（R380）相互作用，以稳定闭合的钳状结构。我们提出，ATP在Hsp90功能中的关键作用是结构性的：ATP作为连接物，物理上连接N和M结构域并稳定其闭合。通过水解切断这一连接可促进重新开放。我们的发现支持R380是一个精氨酸手指（arginine finger）的观点，这是一种在多种NTPase家族中发现的基序，因其与ATP的跨结构域相互作用。这反过来表明，对于某些精氨酸手指而言，核苷酸本身是稳定跨结构域或跨亚基相互作用的重要结构元件。Hsp90作为一种必需的分子伴侣，其功能中ATP的确切作用尚不明确，因为ATP结合而非水解对细胞活力至关重要。本研究作者提出，ATP通过可逆性地稳定Hsp90的闭合构象来发挥结构作用。

期刊

Nature Communications

IF:

15.7

论文数:

9.4W

被引数:

91.2W

机构

National Institute of Diabetes and Digestive and Kidney Diseases

学者数:

论文数: 36

被引数: 8.7K

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