دورية أكاديمية
Refinement of a cryo-EM structure of hERG: Bridging structure and function.
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.) |
References: | ChemMedChem. 2010 Mar 1;5(3):455-67. (PMID: 20104563) J Mol Graph. 1996 Feb;14(1):33-8, 27-8. (PMID: 8744570) J Comput Chem. 2005 Dec;26(16):1781-802. (PMID: 16222654) J Physiol. 1997 Jul 1;502 ( Pt 1):45-60. (PMID: 9234196) J Struct Biol. 2011 Mar;173(3):420-7. (PMID: 20932910) Cell. 2017 Apr 20;169(3):422-430.e10. (PMID: 28431243) J Gen Physiol. 2011 Mar;137(3):315-25. (PMID: 21357734) Eur Biophys J. 2014 Mar;43(2-3):59-69. (PMID: 24362825) Biophys J. 2010 Nov 3;99(9):2841-52. (PMID: 21044581) Front Physiol. 2018 Apr 12;9:207. (PMID: 29706893) Methods. 2009 Oct;49(2):174-80. (PMID: 19398010) J Phys Chem B. 2017 Apr 20;121(15):3718-3723. (PMID: 27936734) Biopolymers. 2012 Sep;97(9):678-86. (PMID: 22696404) Front Pharmacol. 2012 May 08;3:83. (PMID: 22586397) Front Pharmacol. 2020 Jan 24;10:1572. (PMID: 32038248) J Physiol. 2015 Jun 15;593(12):2575-85. (PMID: 25820318) Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13082-7. (PMID: 19651618) Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21. (PMID: 20057044) Nucleic Acids Res. 2007 Jul;35(Web Server issue):W375-83. (PMID: 17452350) J Physiol. 2005 Dec 1;569(Pt 2):367-79. (PMID: 16166152) J Mol Cell Cardiol. 2015 Aug;85:71-8. (PMID: 25986146) Front Pharmacol. 2020 May 04;11:550. (PMID: 32431610) Cell Physiol Biochem. 2008;21(1-3):37-46. (PMID: 18209470) Biophys J. 2008 May 15;94(10):3893-911. (PMID: 18222997) Proc Natl Acad Sci U S A. 2020 Feb 11;117(6):2795-2804. (PMID: 31980532) Elife. 2019 Sep 06;8:. (PMID: 31490124) Proteins. 2010 Nov 1;78(14):2922-34. (PMID: 20740484) J Gen Physiol. 2008 Nov;132(5):507-20. (PMID: 18955593) Biochemistry. 2011 Jul 12;50(27):6146-56. (PMID: 21657256) J Chem Phys. 2005 Feb 1;122(5):54101. (PMID: 15740304) Nat Commun. 2020 Mar 17;11(1):1419. (PMID: 32184399) J Comput Chem. 2008 Aug;29(11):1859-65. (PMID: 18351591) Nat Methods. 2009 Aug;6(8):551-2. (PMID: 19644455) Structure. 2017 Oct 3;25(10):1589-1597.e1. (PMID: 28867613) Sci Rep. 2018 Oct 19;8(1):15494. (PMID: 30341381) J Gen Physiol. 2003 Jun;121(6):599-614. (PMID: 12771194) Physiol Rev. 2012 Jul;92(3):1393-478. (PMID: 22988594) J Membr Biol. 2005 Oct;207(3):169-81. (PMID: 16550488) PLoS Comput Biol. 2009 Feb;5(2):e1000289. (PMID: 19229308) Methods. 2016 May 1;100:50-60. (PMID: 26804562) Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21. (PMID: 20124702) Biophys J. 1994 Feb;66(2 Pt 1):345-54. (PMID: 8161688) Elife. 2019 Nov 27;8:. (PMID: 31774399) J Gen Physiol. 2004 Dec;124(6):703-18. (PMID: 15545400) Bioorg Med Chem Lett. 2005 Mar 15;15(6):1737-41. (PMID: 15745831) Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):E273-82. (PMID: 24379371) J Phys Chem B. 2010 Jun 17;114(23):7830-43. (PMID: 20496934) Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10534-9. (PMID: 12928493) J Gen Physiol. 2013 Sep;142(3):289-303. (PMID: 23980197) Nat Methods. 2017 Jan;14(1):71-73. (PMID: 27819658) J Mol Biol. 2008 Mar 28;377(3):804-18. (PMID: 18280500) Protein Sci. 2020 Jan;29(1):315-329. (PMID: 31724275) Sci Rep. 2016 Oct 12;6:32536. (PMID: 27731415) FEBS Lett. 2005 May 23;579(13):2939-44. (PMID: 15893317) J Gen Physiol. 2019 Feb 4;151(2):231-246. (PMID: 30530765) Trends Pharmacol Sci. 2017 Oct;38(10):899-907. (PMID: 28711156) |
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 |
تدمد: | 1542-0086 |
---|---|
DOI: | 10.1016/j.bpj.2021.01.011 |