Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1126/science.aav4809 |
Structures and gating mechanism of human TRPM2 | |
Wang, Longfei1,2; Fu, Tian-Min1,2; Zhou, Yiming3,4,5; Xia, Shiyu1,2; Greka, Anna3,4,5; Wu, Hao1,2 | |
2018-12-21 | |
发表期刊 | SCIENCE
![]() |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6421页码:1377-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Transient receptor potential (TRP) melastatin 2 (TRPM2) is a cation channel associated with numerous diseases. It has a C-terminal NUDT9 homology (NUDT9H) domain responsible for binding adenosine diphosphate (ADP) ribose (ADPR), and both ADPR and calcium (Ca2+) are required for TRPM2 activation. Here we report cryo electron microscopy structures of human TRPM2 alone, with ADPR, and with ADPR and Ca2+. NUDT9H forms both intra-and intersubunit interactions with the N-terminal TRPM homology region (MHR1/2/3) in the apo state but undergoes conformational changes upon ADPR binding, resulting in rotation of MHR1/2 and disruption of the intersubunit interaction. The binding of Ca2+ further engages transmembrane helices and the conserved TRP helix to cause conformational changes at the MHR arm and the lower gating pore to potentiate channel opening. These findings explain the molecular mechanism of concerted TRPM2 gating by ADPR and Ca2+ and provide insights into the gating mechanism of other TRP channels. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000453845000051 |
WOS关键词 | ION-CHANNEL ; CATION CHANNEL ; ADP-RIBOSE ; SYSTEM ; PORE ; BINDING ; DOMAIN |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/200363 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA; 2.Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA; 3.Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA; 4.Harvard Med Sch, Boston, MA 02115 USA; 5.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA |
推荐引用方式 GB/T 7714 | Wang, Longfei,Fu, Tian-Min,Zhou, Yiming,et al. Structures and gating mechanism of human TRPM2[J]. SCIENCE,2018,362(6421):1377-+. |
APA | Wang, Longfei,Fu, Tian-Min,Zhou, Yiming,Xia, Shiyu,Greka, Anna,&Wu, Hao.(2018).Structures and gating mechanism of human TRPM2.SCIENCE,362(6421),1377-+. |
MLA | Wang, Longfei,et al."Structures and gating mechanism of human TRPM2".SCIENCE 362.6421(2018):1377-+. |
条目包含的文件 | 条目无相关文件。 |
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。
修改评论