Structural Analysis of the UBA Domain of X-linked Inhibitor of Apoptosis Protein Reveals Different Surfaces for Ubiquitin-Binding and Self-Association
文献类型：期刊论文
| 作者 | Tse, MK; Hui, SK; Yang, YH; Yin, ST; Hu, HY; Zou, B; Wong, BCY; Sze, KH |
| 刊名 | PLOS ONE
 |
| 出版日期 | 2011 |
| 卷号 | 6期号:12页码:e28511-e28511 |
| 通讯作者 | Tse, MK (reprint author), Univ Hong Kong, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China.,khsze@hku.hk |
| 英文摘要 | Background: Inhibitor of apoptosis proteins (IAPs) belong to a pivotal antiapoptotic protein family that plays a crucial role in tumorigenesis, cancer progression, chemoresistance and poor patient-survival. X-linked inhibitor of apoptosis protein (XIAP) is a prominent member of IAPs attracting intense research because it has been demonstrated to be a physiological inhibitor of caspases and apoptosis. Recently, an evolutionarily conserved ubiquitin-associated (UBA) domain was identified in XIAP and a number of RING domain-bearing IAPs. This has placed the IAPs in the group of ubiquitin binding proteins. Here, we explore the three-dimensional structure of the XIAP UBA domain (XIAP-UBA) and how it interacts with mono-ubiquitin and diubiquitin conjugates. Principal Findings: The solution structure of the XIAP-UBA domain was determined by NMR spectroscopy. XIAP-UBA adopts a typical UBA domain fold of three tightly packed alpha-helices but with an additional N-terminal 3(10) helix. The XIAP-UBA binds mono-ubiquitin as well as Lys48-linked and linear-linked diubiquitins at low-micromolar affinities. NMR analysis of the XIAP-UBA-ubiquitin interaction reveals that it involves the classical hydrophobic patches surrounding Ile44 of ubiquitin and the conserved MGF/LV motif surfaces on XIAP-UBA. Furthermore, dimerization of XIAP-UBA was observed. Mapping of the self-association surface of XIAP-UBA reveals that the dimerization interface is formed by residues in the N-terminal 3(10) helix, helix alpha 1 and helix alpha 2, separate from the ubiquitin-binding surface. Conclusion: Our results provide the first structural information of XIAP-UBA and map its interaction with mono-ubiquitin, Lys48-linked and linear-linked diubiquitins. The notion that XIAP-UBA uses different surfaces for ubiquitin-binding and self-association provides a plausible model to explain the reported selectivity of XIAP in binding polyubiquitin chains with different linkages. |
| 学科主题 | Science & Technology - Other Topics |
| 类目[WOS] | Multidisciplinary Sciences |
| 关键词[WOS] | NF-KAPPA-B ; LYS48-LINKED POLYUBIQUITIN CHAIN ; CONJUGATING ENZYME E2 ; MEDIATED DIMERIZATION ; CRYSTAL-STRUCTURE ; NMR-SPECTROSCOPY ; BIR DOMAIN ; HIV-1 VPR ; C-CBL ; RECOGNITION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000298370400015 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/869]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Tse, MK,Hui, SK,Yang, YH,et al. Structural Analysis of the UBA Domain of X-linked Inhibitor of Apoptosis Protein Reveals Different Surfaces for Ubiquitin-Binding and Self-Association[J]. PLOS ONE,2011,6(12):e28511-e28511. |
| APA | Tse, MK.,Hui, SK.,Yang, YH.,Yin, ST.,Hu, HY.,...&Sze, KH.(2011).Structural Analysis of the UBA Domain of X-linked Inhibitor of Apoptosis Protein Reveals Different Surfaces for Ubiquitin-Binding and Self-Association.PLOS ONE,6(12),e28511-e28511. |
| MLA | Tse, MK,et al."Structural Analysis of the UBA Domain of X-linked Inhibitor of Apoptosis Protein Reveals Different Surfaces for Ubiquitin-Binding and Self-Association".PLOS ONE 6.12(2011):e28511-e28511. |
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