低温电镜结构揭示了SUMO E1-E2硫酯转移的分子机制。

Anindita Nayak,Digant Nayak,Lijia Jia,Eliza A Ruben,Suryavathi Viswanadhapalli,Priscila Dos Santos Bury,Khaled Mohamed Nassar,Corey H Yu,Anna A Tumanova,Caleb M Stratton,Pirouz Ebadi,Dmitri N Ivanov,Patrick Sung,Ratna K Vadlamudi,Elizabeth V Wasmuth,Shaun K Olsen
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引用次数: 0

摘要

SUMO(小泛素样修饰剂)通过E1、E2和E3三种酶的连续相互作用和活性对蛋白质进行翻译后修饰,从而调节基本的细胞过程。SUMO E1通过两步过程激活SUMO,包括腺苷化和硫酯键形成,随后SUMO转移到其专用的E2酶UBC9。这个过程称为E1-E2硫酯转移(或转硫酯酯化)。尽管SUMO E1-UBC9硫酯转移的分子基础和调控SUMO E1-UBC9特异性的分子规则非常重要,但人们对其知之甚少。在这里,我们展示了人类SUMO E1与UBC9、SUMO1腺苷酸和SUMO1硫酯中间体复合体的低温电镜重建。我们的结构揭示了伴随着硫酯转移的剧烈构象变化,为SUMO E1对UBC9的分子识别提供了见解,并描绘了控制SUMO E1-UBC9特异性的规则。总的来说,我们的结构,生化和基于细胞的研究阐明了SUMOylation发挥其基本生物学功能的分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cryo-EM structures reveal the molecular mechanism of SUMO E1-E2 thioester transfer.
Post-translational modification of proteins by SUMO (small ubiquitin-like modifier) regulates fundamental cellular processes and occurs through the sequential interactions and activities of three enzymes: E1, E2 and E3. SUMO E1 activates SUMO in a two-step process involving adenylation and thioester bond formation, followed by transfer of SUMO to its dedicated E2 enzyme, UBC9. This process is termed E1-E2 thioester transfer (or transthioesterification). Despite its fundamental importance, the molecular basis for SUMO E1-UBC9 thioester transfer and the molecular rules governing SUMO E1-UBC9 specificity are poorly understood. Here we present cryo-EM reconstructions of human SUMO E1 in complex with UBC9, SUMO1 adenylate and SUMO1 thioester intermediate. Our structures reveal drastic conformational changes that accompany thioester transfer, providing insights into the molecular recognition of UBC9 by SUMO E1 and delineating the rules that govern SUMO E1-UBC9 specificity. Collectively, our structural, biochemical and cell-based studies elucidate the molecular mechanisms by which SUMOylation exerts its essential biological functions.
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