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The structural basis of the pH-homeostasis mediated by the Cl - /HCO 3 - exchanger, AE2.

التفاصيل البيبلوغرافية
العنوان: The structural basis of the pH-homeostasis mediated by the Cl - /HCO 3 - exchanger, AE2.
المؤلفون: 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.; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, Shanghai, China., Jian L; Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.; 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., Yao D; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, Shanghai, China.; State Key Laboratory of Oncogenes and Related Genes, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, 200127, Shanghai, China., Rao B; Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, 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; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, Shanghai, China., Li S; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, 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; Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.; 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., Zhao J; Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.; 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., Cao Y; Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China. yu.cao@shsmu.edu.cn.; Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, 200125, Shanghai, China. yu.cao@shsmu.edu.cn.
المصدر: Nature communications [Nat Commun] 2023 Mar 31; Vol. 14 (1), pp. 1812. Date of Electronic Publication: 2023 Mar 31.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Antiporters*/metabolism , Anion Transport Proteins*/metabolism, Humans ; Chloride-Bicarbonate Antiporters ; Hydrogen-Ion Concentration ; Cell Membrane/metabolism ; Homeostasis ; Chlorides/metabolism
مستخلص: 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 HCO 3 - 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.
(© 2023. The Author(s).)
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المشرفين على المادة: 0 (Chloride-Bicarbonate Antiporters)
0 (Antiporters)
0 (Anion Transport Proteins)
0 (Chlorides)
تواريخ الأحداث: Date Created: 20230331 Date Completed: 20230404 Latest Revision: 20230420
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC10066210
DOI: 10.1038/s41467-023-37557-y
PMID: 37002221
قاعدة البيانات: MEDLINE
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