The structure and conformation of Lys63-linked tetraubiquitin.
The structure and conformation of Lys63-linked tetraubiquitin.
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DOI：
10.1016/j.jmb.2009.07.090
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发表时间：
2009-10-09
影响因子：
5.6
通讯作者：
Wolberger, Cynthia
中科院分区：
文献类型：
--
作者：
Datta, Ajit B.;Hura, Greg L.;Wolberger, Cynthia
泛素化涉及泛素C末端通过异肽键共价连接到底物蛋白的赖氨酸侧链。所述修饰可以包含单个泛素部分或通过一个泛素的C末端与下一个泛素中的七个赖氨酸残基之一之间的异肽键连接的泛素分子链。用Lys 63连接的多聚泛素修饰底物蛋白在包括DNA修复和NF-κB活化在内的许多生物学过程中发挥关键的非降解信号传导作用，而由赖氨酸48（Lys 48）连接的链修饰的底物被靶向蛋白酶体进行降解。不同的信号转导特性的替代连接的泛素链大概源于结构差异，可以区分的效应蛋白。我们已经确定了Lys 63 tetraubiquitin的晶体结构，分辨率为1.96 μ m，并进行了小角X射线散射（SAXS）实验和分子动力学（MD）模拟，以探测溶液中Lys 63 tetraubiquitin的构象。该链在晶体中采用高度延伸的构象，与Lys 48 Ub 4的紧凑球形折叠形成对比。小角X射线散射（SAXS）实验表明，四泛素链在溶液中是动态的，采用的构象是更紧凑的比在晶体中的扩展形式的合奏。这些研究结果为理解Lys 63多聚泛素链的行为和识别差异提供了基础。
Ubiquitination involves the covalent attachment of the ubiquitin C-terminus to the lysine sidechain of a substrate protein by an isopeptide bond. The modification can comprise a single ubiquitin moiety or a chain of ubiquitin molecules joined by isopeptide bonds between the C-terminus of one ubiquitin with one of the seven lysine residues in the next ubiquitin. Modification of substrate proteins with Lys63-linked polyubiquitin plays a key non-degradative signaling role in many biological processes including DNA repair and NF-κB activation, whereas substrates modified by lysine-48 (Lys48) linked chains are targeted to the proteasome for degradation. The distinct signaling properties of alternatively linked ubiquitin chains presumably stems from structural differences that can be distinguished by effector proteins. We have determined the crystal structure of Lys63 tetraubiquitin at a resolution of 1.96 Å and performed Small Angle X-ray scattering (SAXS) experiments and molecular dynamics (MD) simulations to probe the conformation of Lys63 tetraubiquitin in solution. The chain adopts a highly extended conformation in the crystal, in contrast with the compact globular fold of Lys48 Ub4. Small Angle X-ray scattering (SAXS) experiments show that the tetraubiquitin chain is dynamic in solution, adopting an ensemble of conformations that are more compact than the extended form in the crystal. The results of these studies provide a basis for understanding the differences in the behavior and recognition of Lys63 polyubiquitin chains.
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影响因子：
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作者：
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DOI：
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