Solution structures of UBA domains reveal a conserved hydrophobic surface for protein-protein interactions
Solution structures of UBA domains reveal a conserved hydrophobic surface for protein-protein interactions
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DOI：
10.1016/s0022-2836(02)00302-9
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发表时间：
2002-06-21
影响因子：
5.6
通讯作者：
Feigon, J
中科院分区：
文献类型：
--
作者：
Mueller, TD;Feigon, J
乌巴结构域是一种常见的类似于45个氨基酸残基的序列基序，其存在于参与泛素/蛋白酶体途径、DNA切除-修复和经由蛋白激酶的细胞信号传导的多种蛋白质中。酵母Rad 23 A（HHR 23 A）的人类同源物是含有内部和C末端乌巴结构域的核苷酸切除修复蛋白的一个实例。HHR 23 A乌巴（2）的溶液结构表明，结构域形成紧密的三螺旋束。我们报道了HHR 23 A的内部乌巴（1）结构域的结构。比较乌巴（1）和乌巴（2）的结构，发现两者形成非常相似的折叠，并具有保守的大疏水表面补丁。乌巴（1）和乌巴（2）之间的结构相似性，尽管它们的序列保守性水平较低，但使我们得出结论，乌巴结构域的结构变异性通常可能相当小。基于结构相似性以及序列保守性分析，我们预测这种疏水表面补丁是存在于不同乌巴结构域中的常见蛋白质相互作用表面。此外，越来越多的证据表明，泛素结合乌巴结构域导致我们预测，疏水表面补丁的乌巴结构域与疏水表面上的五链的P-折叠的泛素。对两个乌巴结构域的详细比较，结合先前的诱变研究，表明HIV-1 Vpr在乌巴上的结合位点（2）与泛素结合位点不完全重叠。(C)2002爱思唯尔科技有限公司版权所有。
UBA domains are a commonly occurring sequence motif of similar to 45 amino acid residues that are found in diverse proteins involved in the ubiquitin/ proteasome pathway, DNA excision-repair, and cell signaling via protein kinases. The human homologue of yeast Rad23A (HHR23A) is one example of a nucleotide excision-repair protein that contains both an internal and a C-terminal UBA domain. The solution structure of HHR23A UBA(2) showed that the domain forms a compact three-helix bundle. We report the structure of the internal UBA(1) domain of HHR23A. Comparison of the structures of UBA(1) and UBA(2) reveals that both form very similar folds and have a conserved large hydrophobic surface patch. The structural similarity between UBA(1) and UBA(2), in spite of their low level of sequence conservation, leads us to conclude that the structural variability of UBA domains in general is likely to be rather small. On the basis of the structural similarities as well as analysis of sequence conservation, we predict that this hydrophobic surface patch is a common protein-interacting surface present in diverse UBA domains. Furthermore, accumulating evidence that ubiquitin binds to UBA domains leads us to the prediction that the hydrophobic surface patch of UBA domains interacts with the hydrophobic surface on the five-stranded P-sheet of ubiquitin. Detailed comparison of the structures of the two UBA domains, combined with previous mutagenesis studies, indicates that the binding site of HIV-1 Vpr on UBA(2) does not completely overlap the ubiquitin binding site. (C) 2002 Elsevier Science Ltd. All rights reserved.