nature20121213-9

来自英国剑桥大学等处的科学家利用单分子FRET技术探测了泛素链的构象动态,结果显示构象选择性是泛素链识别的重要机制。

-2012年12月13日《自然》


中文翻译


【题目】泛素链构象调控相互作用蛋白的识别和活性

【译文】单结构域蛋白中,蛋白识别机制已被广泛研究,但对于动态多结构域系统,该机制界定不清。泛素链是生物学重要多结构域系统,需要通过结构多样的泛素-互作蛋白的识别。 分离的泛素链构象通常不同于泛素-互作蛋白复合物中的构象,表明结合时泛素链发生较大的动态柔性或扩展的链重塑。利用单分子荧光共振能量转移技术,我们发现Lys 63、Lys 48和Met 1相关双泛素存在于几种不同构象状态中。Lys 63和Met 1相关双泛素采取扩展的开放和更加紧凑的关闭构象,且泛素结合结构域和去泛素酶(DUBs)选择了预先存在的构象。相反,Lys 48相关双泛素主要采取紧凑的构象。DUBs直接识别现存的构象,但也可能重塑了泛素链以水解异肽键。Lys 48双泛素化表面的破坏改变了构象动态,并影响DUB活性。因此,泛素链中构象平衡提供了泛素体系中调控的另一层面,而且在不同相关多泛素中观察到的不同构象可能有助于泛素-互作蛋白的特异性。

英文原稿


[Title]: Ubiquitin chain conformation regulates recognition and activity of interacting proteins

[Authors]:Yu Ye,1 Georg Blaser,2 Mathew H. Horrocks,2 Maria J. Ruedas-Rama,3 Shehu Ibrahim,2 Alexander A. Zhukov,2 Angel Orte,3 David Klenerman,2 Sophie E. Jackson2 & David Komander1

[Abstract]:Mechanisms of protein recognition have been extensively studied for single-domain proteins, but are less well characterized for dynamic multidomain systems. Ubiquitin chains represent a biologically important multidomain system that requires recognition by structurally diverse ubiquitin-interacting proteins. Ubiquitin chain conformations in isolation are often different from conformations observed in ubiquitin-interacting protein complexes, indicating either great dynamic flexibility or extensive chain remodelling upon binding. Using single-molecule fluorescence resonance energy transfer, we show that Lys 63-,Lys 48- and Met 1-linked diubiquitin exist in several distinct conformational states in solution.Lys 63- and Met 1-linked diubiquitin adopt extended ‘open’ and more compact ‘closed’ conformations, and ubiquitin-binding domains and deubiquitinases (DUBs) select pre-existing conformations. By contrast,Lys 48-linked diubiquitin adopts predominantly compact conformations. DUBs directly recognize existing conformations, but may also remodel ubiquitin chains to hydrolyse the isopeptide bond. Disruption of theLys 48–diubiquitin interface changes conformational dynamics and affects DUB activity. Hence, conformational equilibria in ubiquitin chains provide an additional layer of regulation in the ubiquitin system, and distinct conformations observed in differently linked polyubiquitin may contribute to the specificity of ubiquitin-interacting proteins.

原文地址

http://www.nature.com/nature/journal/v492/n7428/full/nature11722.html

 

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