Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1

doi:10.7554/eLife.57096

	Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1
	Sun, Demeng 1,4,5; Liu, Sanling 1,5; Li, Siyu 1,5; Zhang, Mengge 1,5; Yang, Fan 1,5; Wen, Ming 1,5; Shi, Pan 1,5; Wang, Tao 3; Pan, Man ; Chang, Shenghai 2
刊名	ELIFE
	2020-09-11
卷号	9
ISSN号	2050-084X
DOI	10.7554/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.
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关键词	PAIN-RELIEVING PEPTIDE ; CHEMICAL-SYNTHESIS ; BINDING-SITE ; PHARMACOLOGY ; LIGATION ; DOMAIN ; VENOM ; CONTRIBUTES ; PLASTICITY ; RECEPTOR
WOS研究方向	Life Sciences & Biomedicine - Other Topics
语种	英语
出版者	ELIFE SCIENCES PUBLICATIONS LTD
WOS记录号	WOS:000580904600001
资助机构	National Key Research and Development ; National Natural Science Foundation of China ; Chinese Academy of Sciences
内容类型	期刊论文
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, Hefei Natl Lab Phys Sci Microscale, Anhui Lab Adv Photon Sci & Technol, Hefei, Peoples R China 2.Zhejiang Univ, Sch Med, Hangzhou, Peoples R China 3.Chinese Acad Sci, High Field Magnet Lab, Hefei, Peoples R China 4.Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Key Lab Bioorgan Phosphorus Chem & Chem Biol, Minist Educ,Dept Chem, Beijing, Peoples R China 5.Univ Sci & Technol China, Sch Life Sci, Hefei, 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).