PMID- 34129834
OWN - NLM
STAT- MEDLINE
DCOM- 20220316
LR  - 20240214
IS  - 1878-4186 (Electronic)
IS  - 0969-2126 (Print)
IS  - 0969-2126 (Linking)
VI  - 29
IP  - 9
DP  - 2021 Sep 2
TI  - Cryo-EM structure of an open conformation of a gap junction hemichannel in lipid 
      bilayer nanodiscs.
PG  - 1040-1047.e3
LID - S0969-2126(21)00168-4 [pii]
LID - 10.1016/j.str.2021.05.010 [doi]
AB  - To mediate cell-to-cell communication via gap junction channels (GJCs), connexins 
      (Cx) traffic as hexameric hemichannels to the plasma membrane, which dock 
      end-to-end between adjacent cell membranes, thereby forming a dodecameric 
      intercellular conduit. Hemichannels also function independently to mediate the 
      passage of contents between the cytoplasm and extracellular space. To generate 
      hemichannels, the mutation N176Y was introduced into the second extracellular 
      loop of Cx26. The electron cryomicroscopy structure of the hexameric hemichannel 
      in lipid bilayer nanodiscs displays an open pore and a 4-helix bundle 
      transmembrane design that is nearly identical to dodecameric GJCs. In contrast to 
      the high resolution of the transmembrane alpha-helices, the extracellular loops are 
      less well resolved. The conformational flexibility of the extracellular loops may 
      be essential to facilitate surveillance of hemichannels in apposed cells to 
      identify compatible Cx isoforms that enable intercellular docking. Our results 
      also provide a structural foundation for previous electrophysiologic and 
      permeation studies of Cx hemichannels.
CI  - Copyright (c) 2021. Published by Elsevier Ltd.
FAU - Khan, Ali K
AU  - Khan AK
AD  - Department of Molecular Physiology and Biological Physics, University of Virginia 
      School of Medicine, Sheridan G. Snyder Translational Research Building, Rm 320, 
      480 Ray C. Hunt Drive, Charlottesville, VA 22908, USA.
FAU - Jagielnicki, Maciej
AU  - Jagielnicki M
AD  - Department of Molecular Physiology and Biological Physics, University of Virginia 
      School of Medicine, Sheridan G. Snyder Translational Research Building, Rm 320, 
      480 Ray C. Hunt Drive, Charlottesville, VA 22908, USA.
FAU - Bennett, Brad C
AU  - Bennett BC
AD  - Department of Molecular Physiology and Biological Physics, University of Virginia 
      School of Medicine, Sheridan G. Snyder Translational Research Building, Rm 320, 
      480 Ray C. Hunt Drive, Charlottesville, VA 22908, USA.
FAU - Purdy, Michael D
AU  - Purdy MD
AD  - Department of Molecular Physiology and Biological Physics, University of Virginia 
      School of Medicine, Sheridan G. Snyder Translational Research Building, Rm 320, 
      480 Ray C. Hunt Drive, Charlottesville, VA 22908, USA.
FAU - Yeager, Mark
AU  - Yeager M
AD  - Department of Molecular Physiology and Biological Physics, University of Virginia 
      School of Medicine, Sheridan G. Snyder Translational Research Building, Rm 320, 
      480 Ray C. Hunt Drive, Charlottesville, VA 22908, USA; Center for Membrane 
      Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, 
      USA; Cardiovascular Research Center, University of Virginia School of Medicine, 
      Charlottesville, VA 22908, USA; Department of Medicine, Division of 
      Cardiovascular Medicine, University of Virginia School of Medicine, 
      Charlottesville, VA 22908, USA. Electronic address: yeager@virginia.edu.
LA  - eng
GR  - R01 GM138532/GM/NIGMS NIH HHS/United States
GR  - P41 GM103311/GM/NIGMS NIH HHS/United States
GR  - G20 RR031199/RR/NCRR NIH HHS/United States
GR  - R01 HL048908/HL/NHLBI NIH HHS/United States
GR  - S10 OD018149/OD/NIH HHS/United States
GR  - S10 RR025067/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210614
PL  - United States
TA  - Structure
JT  - Structure (London, England : 1993)
JID - 101087697
RN  - 0 (GJB2 protein, human)
RN  - 0 (Lipid Bilayers)
RN  - 127120-53-0 (Connexin 26)
SB  - IM
MH  - Connexin 26/*chemistry
MH  - Humans
MH  - Lipid Bilayers/chemistry
MH  - Molecular Dynamics Simulation
MH  - Protein Conformation, alpha-Helical
PMC - PMC9616683
MID - NIHMS1843062
OTO - NOTNLM
OT  - connexins
OT  - cryo-EM
OT  - gap junction hemichannels
OT  - membrane proteins
OT  - protein structure
COIS- Declaration of interests The authors declare that they have no competing 
      interests.
EDAT- 2021/06/16 06:00
MHDA- 2022/03/17 06:00
PMCR- 2022/10/28
CRDT- 2021/06/15 20:11
PHST- 2020/06/01 00:00 [received]
PHST- 2021/02/26 00:00 [revised]
PHST- 2021/05/14 00:00 [accepted]
PHST- 2021/06/16 06:00 [pubmed]
PHST- 2022/03/17 06:00 [medline]
PHST- 2021/06/15 20:11 [entrez]
PHST- 2022/10/28 00:00 [pmc-release]
AID - S0969-2126(21)00168-4 [pii]
AID - 10.1016/j.str.2021.05.010 [doi]
PST - ppublish
SO  - Structure. 2021 Sep 2;29(9):1040-1047.e3. doi: 10.1016/j.str.2021.05.010. Epub 
      2021 Jun 14.