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Cryo-EM structure of a eukaryotic zinc transporter at a low pH suggests its Zn2+-releasing mechanism.
Zhang, Senfeng; Fu, Chunting; Luo, Yongbo; Xie, Qingrong; Xu, Tong; Sun, Ziyi; Su, Zhaoming; Zhou, Xiaoming.
Afiliação
  • Zhang S; Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • Fu C; Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • Luo Y; The State Key Laboratory of Biotherapy, Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • Xie Q; Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • Xu T; Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • Sun Z; Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: ziyi.sun@scu.edu.cn.
  • Su Z; The State Key Laboratory of Biotherapy, Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: zsu@scu.edu.cn.
  • Zhou X; Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: x.zhou@scu.edu.cn.
J Struct Biol ; 215(1): 107926, 2023 03.
Article em En | MEDLINE | ID: mdl-36464198
Zinc transporter 8 (ZnT8) is mainly expressed in pancreatic islet ß cells and is responsible for H+-coupled uptake (antiport) of Zn2+ into the lumen of insulin secretory granules. Structures of human ZnT8 and its prokaryotic homolog YiiP have provided structural basis for constructing a plausible transport cycle for Zn2+. However, the mechanistic role that protons play in the transport process remains unclear. Here we present a lumen-facing cryo-EM structure of ZnT8 from Xenopus tropicalis (xtZnT8) in the presence of Zn2+ at a luminal pH (5.5). Compared to a Zn2+-bound xtZnT8 structure at a cytosolic pH (7.5), the low-pH structure displays an empty transmembrane Zn2+-binding site with a disrupted coordination geometry. Combined with a Zn2+-binding assay our data suggest that protons may disrupt Zn2+ coordination at the transmembrane Zn2+-binding site in the lumen-facing state, thus facilitating Zn2+ release from ZnT8 into the lumen.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Prótons / Eucariotos Limite: Humans Idioma: En Revista: J Struct Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Prótons / Eucariotos Limite: Humans Idioma: En Revista: J Struct Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China