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The structural basis of the pH-homeostasis mediated by the Cl-/HCO3- exchanger, AE2.
Zhang, Qing; Jian, Liyan; Yao, Deqiang; Rao, Bing; Xia, Ying; Hu, Kexin; Li, Shaobai; Shen, Yafeng; Cao, Mi; Qin, An; Zhao, Jie; Cao, Yu.
Afiliação
  • Zhang Q; Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.
  • Jian L; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, Shanghai, China.
  • Yao D; Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.
  • Rao B; Department of Orthopaedics, Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.
  • Xia Y; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, Shanghai, China.
  • Hu K; State Key Laboratory of Oncogenes and Related Genes, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, 200127, Shanghai, China.
  • Li S; Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.
  • Shen Y; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, Shanghai, China.
  • Cao M; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, Shanghai, China.
  • Qin A; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, Shanghai, China.
  • Zhao J; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, Shanghai, China.
  • Cao Y; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, Shanghai, China.
Nat Commun ; 14(1): 1812, 2023 03 31.
Article em En | MEDLINE | ID: mdl-37002221
The cell maintains its intracellular pH in a narrow physiological range and disrupting the pH-homeostasis could cause dysfunctional metabolic states. Anion exchanger 2 (AE2) works at high cellular pH to catalyze the exchange between the intracellular HCO3- and extracellular Cl-, thereby maintaining the pH-homeostasis. Here, we determine the cryo-EM structures of human AE2 in five major operating states and one transitional hybrid state. Among those states, the AE2 shows the inward-facing, outward-facing, and intermediate conformations, as well as the substrate-binding pockets at two sides of the cell membrane. Furthermore, critical structural features were identified showing an interlock mechanism for interactions among the cytoplasmic N-terminal domain and the transmembrane domain and the self-inhibitory effect of the C-terminal loop. The structural and cell-based functional assay collectively demonstrate the dynamic process of the anion exchange across membranes and provide the structural basis for the pH-sensitive pH-rebalancing activity of AE2.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antiporters / Proteínas de Transporte de Ânions Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antiporters / Proteínas de Transporte de Ânions Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China País de publicação: Reino Unido