Noncovalent dimerization of ubiquitin.

Noncovalent dimerization of ubiquitin.
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DOI:
10.1002/anie.201106190
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发表时间:
2012-01-09
影响因子:
16.6
通讯作者:
Tang, Chun
Tang, Chun
中科院分区:
化学1区
文献类型:
--
作者:
Liu, Zhu;Zhang, Wei-Ping;Xing, Qiong;Ren, Xuefeng;Liu, Maili;Tang, Chun

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泛素是细胞中的一种小分子信号蛋白,在真核生物中高度保守。遍在蛋白与无数包含一个或多个遍在蛋白结合结构域(UBD)的伴侣蛋白相互作用。为了实现与几个UBD的多价结合,泛素通常通过一个泛素的C-末端羧基和另一个泛素的伯胺之间的异肽键共价连接;[1a,B]二泛素中的两个亚基分别被称为近端单元和远端单元。所有七个赖氨酸和泛素的N-末端可以参与异肽键。[2]多个泛素可以串联起来形成聚泛素。根据连接位点的不同,二聚和聚(泛素)可以显示不同的四级结构,这可能是它们连接特异性功能的原因。[1a在这些连接中,Lys 11、Lys 48和Lys 63-连接的聚(遍在蛋白)被最好地表征:Lys 63-连接的聚(遍在蛋白)参与细胞事件,如内吞作用和DNA修复,而Lys 11-和Lys 48-连接的聚(遍在蛋白)都可以发出蛋白体降解的信号。[1a,B]在晶体中,Lys 48连接的双泛素大多采用闭合构象,在两个亚基中掩埋Ile 44周围的疏水残基[3a,B,4]; Lys 63连接的双泛素采用开放延伸结构[5a,B,6]而Lys 11连接的双泛素显示中间亚基分离。[7、8]
Ubiquitin is a small signaling protein in cells and is highly conserved throughout the eukaryotes. Ubiquitin interacts with myriad partner proteins that contain one or more ubiquitin-binding domains (UBDs). To achieve multivalent binding with several UBDs, ubiquitins are often covalently linked by an isopeptide bond between the C-terminal carboxyl group of one ubiquitin and a primary amine in another;[1a, b] the two subunits in a di-ubiquitin are referred to as the proximal unit and the distal unit, respectively. All seven lysines and the N-terminus of ubiquitin can participate in the isopeptide bond.[2] In tandem, multiple ubiquitins can be linked up to form a poly (ubiquitin). Depending on the site of the linkage, di-and poly (ubiquitin) s can display distinct quaternary structures, which may account for their linkage-specific functions.[1a, b] Among the linkages, Lys11, Lys48, and Lys63-linked poly (ubiquitin) s are best characterized: Lys63-linked poly (ubiquitin) is involved in cellular events such as endocytosis and DNA repair, while both Lys11-and Lys48-linked poly (ubiquitin) s can signal for proteosomal degradation.[1a, b] In crystal, Lys48-linked diubiquitin mostly adopts a closed conformation, burying hydrophobic residues around Ile44 in both subunits;[3a, b, 4] Lys63-linked di-ubiquitin adopts an open extended structure;[5a, b, 6] while Lys11-linked di-ubiquitin displays intermediate subunit separation.[7, 8]
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