Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation.

Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation.
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DOI:
10.1038/embor.2011.21
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发表时间:
2011-04
期刊:
影响因子:
7.7
通讯作者:
Polo, Simona
Polo, Simona
中科院分区:
生物学2区
文献类型:
--
作者:
Maspero, Elena;Mari, Sara;Valentini, Eleonora;Musacchio, Andrea;Fish, Alexander;Pasqualato, Sebastiano;Polo, Simona

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几种机制已经提出了合成底物连接的泛素链。HECT连接酶直接催化蛋白质泛素化,并被发现与泛素非共价相互作用。我们报道了Nedd4 HECT结构域的晶体结构,无论是单独的还是与泛素复合的,都显示出一种新的结合模式,涉及泛素上的两个表面和HECT n -叶的两个亚结构域。这些结构提示了一种hect到底物泛素转移的模型,在这种模型中,底物上的生长链保持在靠近催化半胱氨酸的位置,以促进加工能力。突变分析强调了底物多泛素化和自身泛素化过程之间的差异。
Several mechanisms have been proposed for the synthesis of substrate-linked ubiquitin chains. HECT ligases directly catalyse protein ubiquitination and have been found to non-covalently interact with ubiquitin. We report crystal structures of the Nedd4 HECT domain, alone and in complex with ubiquitin, which show a new binding mode involving two surfaces on ubiquitin and both subdomains of the HECT N-lobe. The structures suggest a model for HECT-to-substrate ubiquitin transfer, in which the growing chain on the substrate is kept close to the catalytic cysteine to promote processivity. Mutational analysis highlights differences between the processes of substrate polyubiquitination and self-ubiquitination.
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