Ubiquitin Recognition by the DNA Repair Protein hHR23a

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• 作者：Qinghua Wang ; Amanda M. Goh ; Peter M. Howley ; and Kylie J. Walters
• 刊名：Biochemistry
• 出版年：2003
• 出版时间：November 25, 2003
• 年：2003
• 卷：42
• 期：46
• 页码：13529 - 13535
• 全文大小：854K
• 年卷期：v.42,no.46(November 25, 2003)
• ISSN：1520-4995

文摘

Ubiquitin is a prominent regulatory protein in numerous biological processes, including targetedprotein degradation, endocytic sorting, transcriptional control, intranuclear localization, and retroviral virionbudding. Ubiquitin-associated (UBA) domains, ubiquitin interacting motifs (UIM), and coupling of ubiquitinconjugation to ER degradation (CUE) motifs have been identified as ubiquitin receptors. The DNA repairprotein hHR23a has two UBA domains that can each bind ubiquitin in addition to an N-terminal UBLdomain that binds S5a and S2, two components of the 26S proteasome. Here we reveal hHR23a recognizesubiquitin through a predominately hydrophobic surface formed by residues within mages/gifchars/alpha.gif" BORDER=0>1 and mages/gifchars/alpha.gif" BORDER=0>3 of each ofits UBA domains. These two UBA surfaces bind a region on ubiquitin that includes K48. These findingshave implications for published studies revealing that hHR23a inhibits K48-linked polyubiquitin chainformation. In addition, by using ¹⁵N NMR relaxation experiments, we find that binding ubiquitin requiresa structural change in hHR23a. HHR23 proteins are hypothesized to link ubiquitin to S5a, and we providedirect evidence that hHR23 could form a ternary complex with ubiquitin and S5a.