PMID- 37647412
OWN - NLM
STAT- MEDLINE
DCOM- 20230901
LR  - 20231213
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 9
IP  - 35
DP  - 2023 Sep
TI  - Structures of wild-type and selected CMT1X mutant connexin 32 gap junction 
      channels and hemichannels.
PG  - eadh4890
LID - 10.1126/sciadv.adh4890 [doi]
LID - eadh4890
AB  - In myelinating Schwann cells, connection between myelin layers is mediated by gap 
      junction channels (GJCs) formed by docked connexin 32 (Cx32) hemichannels (HCs). 
      Mutations in Cx32 cause the X-linked Charcot-Marie-Tooth disease (CMT1X), a 
      degenerative neuropathy without a cure. A molecular link between Cx32 dysfunction 
      and CMT1X pathogenesis is still missing. Here, we describe the high-resolution 
      cryo-electron cryo-myography (cryo-EM) structures of the Cx32 GJC and HC, along 
      with two CMT1X-linked mutants, W3S and R22G. While the structures of wild-type 
      and mutant GJCs are virtually identical, the HCs show a major difference: In the 
      W3S and R22G mutant HCs, the amino-terminal gating helix partially occludes the 
      pore, consistent with a diminished HC activity. Our results suggest that HC 
      dysfunction may be involved in the pathogenesis of CMT1X.
FAU - Qi, Chao
AU  - Qi C
AUID- ORCID: 0000-0003-1277-0363
AD  - Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
AD  - Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, 
      Switzerland.
FAU - Lavriha, Pia
AU  - Lavriha P
AUID- ORCID: 0009-0007-6046-0868
AD  - Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
AD  - Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, 
      Switzerland.
FAU - Bayraktar, Erva
AU  - Bayraktar E
AUID- ORCID: 0000-0002-9660-5535
AD  - Veneto Institute of Molecular Medicine (VIMM), Padua, Italy.
AD  - Department of Physics and Astronomy "G. Galilei", University of Padua, Padua, 
      Italy.
FAU - Vaithia, Anand
AU  - Vaithia A
AUID- ORCID: 0000-0002-7568-0181
AD  - Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
AD  - Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, 
      Switzerland.
FAU - Schuster, Dina
AU  - Schuster D
AUID- ORCID: 0000-0001-6611-8237
AD  - Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
AD  - Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, 
      Switzerland.
AD  - Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
FAU - Pannella, Micaela
AU  - Pannella M
AD  - Veneto Institute of Molecular Medicine (VIMM), Padua, Italy.
AD  - Department of Physics and Astronomy "G. Galilei", University of Padua, Padua, 
      Italy.
FAU - Sala, Valentina
AU  - Sala V
AUID- ORCID: 0009-0007-9842-9807
AD  - Veneto Institute of Molecular Medicine (VIMM), Padua, Italy.
FAU - Picotti, Paola
AU  - Picotti P
AD  - Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
FAU - Bortolozzi, Mario
AU  - Bortolozzi M
AUID- ORCID: 0000-0001-7198-9838
AD  - Veneto Institute of Molecular Medicine (VIMM), Padua, Italy.
AD  - Department of Physics and Astronomy "G. Galilei", University of Padua, Padua, 
      Italy.
FAU - Korkhov, Volodymyr M
AU  - Korkhov VM
AUID- ORCID: 0000-0002-0962-9433
AD  - Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
AD  - Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, 
      Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20230830
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
RN  - 0 (Connexins)
RN  - 0 (Ion Channels)
SB  - IM
MH  - Humans
MH  - *Connexins/genetics
MH  - Ion Channels
MH  - *Charcot-Marie-Tooth Disease/genetics
MH  - Gap Junctions/genetics
MH  - Gap Junction beta-1 Protein
PMC - PMC10468125
EDAT- 2023/08/30 18:42
MHDA- 2023/09/01 06:43
PMCR- 2023/08/30
CRDT- 2023/08/30 14:05
PHST- 2023/09/01 06:43 [medline]
PHST- 2023/08/30 18:42 [pubmed]
PHST- 2023/08/30 14:05 [entrez]
PHST- 2023/08/30 00:00 [pmc-release]
AID - adh4890 [pii]
AID - 10.1126/sciadv.adh4890 [doi]
PST - ppublish
SO  - Sci Adv. 2023 Sep;9(35):eadh4890. doi: 10.1126/sciadv.adh4890. Epub 2023 Aug 30.