دورية أكاديمية
أعرض في EDS

Refinement of a cryo-EM structure of hERG: Bridging structure and function.

التفاصيل البيبلوغرافية
العنوان: Refinement of a cryo-EM structure of hERG: Bridging structure and function.
المؤلفون: Khan HM; Centre for Molecular Simulation, Department of Biological Sciences, Faculty of Science, University of Calgary, Calgary, Alberta, Canada., Guo J; Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Duff HJ; Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Tieleman DP; Centre for Molecular Simulation, Department of Biological Sciences, Faculty of Science, University of Calgary, Calgary, Alberta, Canada., Noskov SY; Centre for Molecular Simulation, Department of Biological Sciences, Faculty of Science, University of Calgary, Calgary, Alberta, Canada. Electronic address: snoskov@ucalgary.ca.
المصدر: Biophysical journal [Biophys J] 2021 Feb 16; Vol. 120 (4), pp. 738-748. Date of Electronic Publication: 2021 Jan 19.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 0370626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1542-0086 (Electronic) Linking ISSN: 00063495 NLM ISO Abbreviation: Biophys J Subsets: MEDLINE
أسماء مطبوعة: Publication: Cambridge, MA : Cell Press
Original Publication: New York, Published by Rockefeller University Press [etc.] for the Biophysical Society.
مواضيع طبية MeSH: Ether-A-Go-Go Potassium Channels*/metabolism , Molecular Dynamics Simulation*, Action Potentials ; Cryoelectron Microscopy ; ERG1 Potassium Channel/metabolism ; Humans
مستخلص: The human-ether-a-go-go-related gene (hERG) encodes the voltage-gated potassium channel (KCNH2 or Kv11.1, commonly known as hERG). This channel plays a pivotal role in the stability of phase 3 repolarization of the cardiac action potential. Although a high-resolution cryo-EM structure is available for its depolarized (open) state, the structure surprisingly did not feature many functionally important interactions established by previous biochemical and electrophysiology experiments. Using molecular dynamics flexible fitting (MDFF), we refined the structure and recovered the missing functionally relevant salt bridges in hERG in its depolarized state. We also performed electrophysiology experiments to confirm the functional relevance of a novel salt bridge predicted by our refinement protocol. Our work shows how refinement of a high-resolution cryo-EM structure helps to bridge the existing gap between the structure and function in the voltage-sensing domain (VSD) of hERG.
(Copyright © 2021 Biophysical Society. Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01 GM116961 United States GM NIGMS NIH HHS; R01 HL128537 United States HL NHLBI NIH HHS; FRN-CIHR 156236 Canada CIHR
المشرفين على المادة: 0 (ERG1 Potassium Channel)
0 (Ether-A-Go-Go Potassium Channels)
تواريخ الأحداث: Date Created: 20210121 Date Completed: 20210531 Latest Revision: 20220218
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7896098
DOI: 10.1016/j.bpj.2021.01.011
PMID: 33476597
قاعدة البيانات: MEDLINE
الوصف
تدمد:1542-0086
DOI:10.1016/j.bpj.2021.01.011