中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1

文献类型:期刊论文

作者Sun, Demeng1,2,3; Liu, Sanling1,2; Li, Siyu1,2; Zhang, Mengge1,2; Yang, Fan1,2; Wen, Ming1,2; Shi, Pan1,2; Wang, Tao4; Pan, Man; Chang, Shenghai5
刊名ELIFE
出版日期2020-09-11
卷号9
ISSN号2050-084X
DOI10.7554/eLife.57096
通讯作者Zhang, Longhua(zlhustc@ustc.edu.cn) ; Tian, Changlin(cltian@ustc.edu.cn) ; Liu, Lei(lliu@mail.tsinghua.edu.cn)
英文摘要Acid-sensing ion channels (ASICs) are proton-gated cation channels that are involved in diverse neuronal processes including pain sensing. The peptide toxin Mambalgin1 (Mamba1) from black mamba snake venom can reversibly inhibit the conductance of ASICs, causing an analgesic effect. However, the detailed mechanism by which Mamba1 inhibits ASIC1s, especially how Mamba1 binding to the extracellular domain affects the conformational changes of the transmembrane domain of ASICs remains elusive. Here, we present single-particle cryo-EM structures of human ASIC1a (hASIC1a) and the hASIC1a-Mamba1 complex at resolutions of 3.56 and 3.90 angstrom, respectively. The structures revealed the inhibited conformation of hASIC1a upon Mamba1 binding. The combination of the structural and physiological data indicates that Mamba1 preferentially binds hASIC1a in a closed state and reduces the proton sensitivity of the channel, representing a closed-state trapping mechanism.
WOS关键词PAIN-RELIEVING PEPTIDE ; CHEMICAL-SYNTHESIS ; BINDING-SITE ; PHARMACOLOGY ; LIGATION ; DOMAIN ; VENOM ; CONTRIBUTES ; PLASTICITY ; RECEPTOR
资助项目National Key Research and Development[2017YFA0505201] ; National Key Research and Development[2016YFA0400903] ; National Key Research and Development[2017YFA0505403] ; National Natural Science Foundation of China[31600601] ; National Natural Science Foundation of China[91753205] ; National Natural Science Foundation of China[21778051] ; Chinese Academy of Sciences[GJHZ201946]
WOS研究方向Life Sciences & Biomedicine - Other Topics
语种英语
WOS记录号WOS:000580904600001
出版者ELIFE SCIENCES PUBLICATIONS LTD
资助机构National Key Research and Development ; National Natural Science Foundation of China ; Chinese Academy of Sciences
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/104678]  
专题中国科学院合肥物质科学研究院
通讯作者Zhang, Longhua; Tian, Changlin; Liu, Lei
作者单位1.Univ Sci & Technol China, Sch Life Sci, Hefei, Peoples R China
2.Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Anhui Lab Adv Photon Sci & Technol, Hefei, Peoples R China
3.Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Key Lab Bioorgan Phosphorus Chem & Chem Biol, Minist Educ,Dept Chem, Beijing, Peoples R China
4.Chinese Acad Sci, High Field Magnet Lab, Hefei, Peoples R China
5.Zhejiang Univ, Sch Med, Hangzhou, Peoples R China
推荐引用方式
GB/T 7714
Sun, Demeng,Liu, Sanling,Li, Siyu,et al. Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1[J]. ELIFE,2020,9.
APA Sun, Demeng.,Liu, Sanling.,Li, Siyu.,Zhang, Mengge.,Yang, Fan.,...&Liu, Lei.(2020).Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1.ELIFE,9.
MLA Sun, Demeng,et al."Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1".ELIFE 9(2020).

入库方式: OAI收割

来源:合肥物质科学研究院

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