Solution Structure of Human SUMO-3 C47S and Its Binding Surface for Ubc9

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• 作者：Husheng Ding ; Yingqi Xu ; Quan Chen ; Haiming Dai ; Yajun Tang ; Jihui Wu ; and Yunyu Shi
• 刊名：Biochemistry
• 出版年：2005
• 出版时间：March 1, 2005
• 年：2005
• 卷：44
• 期：8
• 页码：2790 - 2799
• 全文大小：571K
• 年卷期：v.44,no.8(March 1, 2005)
• ISSN：1520-4995

文摘

Small ubiquitin-related modifier SUMO-3 is a member of a growing family of ubiquitin-likeproteins (Ubls). So far, four isoforms of SUMO have been identified in humans. It is generally knownthat SUMO modification regulates protein localization and activity. Previous structure and function studieshave been mainly focused on SUMO-1. The sequence of SUMO-3 is 46% identical with that of SUMO-1; nevertheless, functional heterogeneity has been found between the two homologues. Here we reportthe solution structure of SUMO-3 C47S (residues 14-92) featuring the ------ ubiquitin fold.Structural comparison shows that SUMO-3 C47S resembles ubiquitin more than SUMO-1. On the helix-sheet interface, a strong hydrophobic interaction contributes to formation of the globular and compactfold. A Gly-Gly motif at the C-terminal tail, extending away from the core structure, is accessible toenzymes and substrates. In vivo, SUMO modification proceeds via a multistep pathway, and Ubc9 playsan indispensable role as the SUMO conjugating enzyme (E2) in this process. To develop a betterunderstanding of SUMO-3 conjugation, the Ubc9 binding surface on SUMO-3 C47S has been detectedby chemical shift perturbation using NMR spectroscopy. The binding site mainly resides on the hydrophilicside of the -sheet. Negatively charged and hydrophobic residues of this region are highly or moderatelyconserved among SUMO family members. Notably, the negatively charged surface of SUMO-3 C47S ishighly complementary in its electrostatic potentials and hydrophobicity to the positively charged surfaceof Ubc9. This work indicates dissimilarities between SUMO-3 and SUMO-1 in tertiary structure andprovides insight into the specific interactions of SUMO-3 with its modifying enzyme.