Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5
文献类型：期刊论文
| 作者 | Zhang, Zhe1; Zhang, Tianlong1; Wang, Shanshan1; Gong, Zhou2; Tang, Chun2; Chen, Jiangye1; Ding, Jianping1 |
| 刊名 | ELIFE
 |
| 出版日期 | 2014-06-23 |
| 卷号 | 3 |
| 英文摘要 | Rabex-5 and Rabaptin-5 function together to activate Rab5 and further promote early endosomal fusion in endocytosis. The Rabex-5 GEF activity is autoinhibited by the Rabex-5 CC domain (Rabex-5CC) and activated by the Rabaptin-5 C2-1 domain (Rabaptin-5C21) with yet unknown mechanism. We report here the crystal structures of Rabex-5 in complex with the dimeric Rabaptin-5C21 (Rabaptin-5C212) and in complex with Rabaptin-5C212 and Rab5, along with biophysical and biochemical analyses. We show that Rabex-5CC assumes an amphipathic a-helix which binds weakly to the substrate-binding site of the GEF domain, leading to weak autoinhibition of the GEF activity. Binding of Rabaptin-5C21 to Rabex-5 displaces Rabex-5CC to yield a largely exposed substrate-binding site, leading to release of the GEF activity. In the ternary complex the substrate-binding site of Rabex-5 is completely exposed to bind and activate Rab5. Our results reveal the molecular mechanism for the regulation of the Rabex-5 GEF activity. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Biology |
| 研究领域[WOS] | Life Sciences & Biomedicine - Other Topics |
| 关键词[WOS] | EXCHANGE FACTOR RABEX-5 ; NUCLEOTIDE-EXCHANGE ; RAB GTPASES ; CRYSTAL-STRUCTURE ; STRUCTURAL BASIS ; BINDING DOMAINS ; EARLY ENDOSOMES ; FINGER DOMAIN ; EFFECTOR ; ENDOCYTOSIS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000338725500002 |
| 公开日期 | 2015-07-14 |
| 源URL | [http://ir.wipm.ac.cn/handle/112942/1350]  |
| 专题 | 武汉物理与数学研究所_磁共振应用研究部 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Zhe,Zhang, Tianlong,Wang, Shanshan,et al. Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5[J]. ELIFE,2014,3. |
| APA | Zhang, Zhe.,Zhang, Tianlong.,Wang, Shanshan.,Gong, Zhou.,Tang, Chun.,...&Ding, Jianping.(2014).Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5.ELIFE,3. |
| MLA | Zhang, Zhe,et al."Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5".ELIFE 3(2014). |
入库方式： OAI收割
来源：武汉物理与数学研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。