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Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1.
Sun, Demeng; Liu, Sanling; Li, Siyu; Zhang, Mengge; Yang, Fan; Wen, Ming; Shi, Pan; Wang, Tao; Pan, Man; Chang, Shenghai; Zhang, Xing; Zhang, Longhua; Tian, Changlin; Liu, Lei.
Afiliación
  • Sun D; Hefei National Laboratory of Physical Sciences at Microscale, Anhui Laboratory of Advanced Photonic Science and Technology and School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • Liu S; Tsinghua-Peking Joint Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, China.
  • Li S; Hefei National Laboratory of Physical Sciences at Microscale, Anhui Laboratory of Advanced Photonic Science and Technology and School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • Zhang M; Hefei National Laboratory of Physical Sciences at Microscale, Anhui Laboratory of Advanced Photonic Science and Technology and School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • Yang F; Hefei National Laboratory of Physical Sciences at Microscale, Anhui Laboratory of Advanced Photonic Science and Technology and School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • Wen M; Hefei National Laboratory of Physical Sciences at Microscale, Anhui Laboratory of Advanced Photonic Science and Technology and School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • Shi P; Hefei National Laboratory of Physical Sciences at Microscale, Anhui Laboratory of Advanced Photonic Science and Technology and School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • Wang T; Hefei National Laboratory of Physical Sciences at Microscale, Anhui Laboratory of Advanced Photonic Science and Technology and School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • Pan M; High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, China.
  • Chang S; Tsinghua-Peking Joint Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, China.
  • Zhang X; School of Medicine, Zhejiang University, Hangzhou, China.
  • Zhang L; School of Medicine, Zhejiang University, Hangzhou, China.
  • Tian C; Hefei National Laboratory of Physical Sciences at Microscale, Anhui Laboratory of Advanced Photonic Science and Technology and School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • Liu L; Hefei National Laboratory of Physical Sciences at Microscale, Anhui Laboratory of Advanced Photonic Science and Technology and School of Life Sciences, University of Science and Technology of China, Hefei, China.
Elife ; 92020 09 11.
Article en En | MEDLINE | ID: mdl-32915133
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 Å, 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Venenos Elapídicos / Canales Iónicos Sensibles al Ácido Límite: Animals / Humans Idioma: En Revista: Elife Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Venenos Elapídicos / Canales Iónicos Sensibles al Ácido Límite: Animals / Humans Idioma: En Revista: Elife Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido