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Structure paper

TitleConformational changes and CO-induced channel gating in connexin26.
Journal, issue, pagesStructure, Vol. 30, Issue 5, Page 697-706.e4, Year 2022
Publish dateMay 5, 2022
AuthorsDeborah H Brotherton / Christos G Savva / Timothy J Ragan / Nicholas Dale / Alexander D Cameron /
PubMed AbstractConnexins form large-pore channels that function either as dodecameric gap junctions or hexameric hemichannels to allow the regulated movement of small molecules and ions across cell membranes. ...Connexins form large-pore channels that function either as dodecameric gap junctions or hexameric hemichannels to allow the regulated movement of small molecules and ions across cell membranes. Opening or closing of the channels is controlled by a variety of stimuli, and dysregulation leads to multiple diseases. An increase in the partial pressure of carbon dioxide (PCO) has been shown to cause connexin26 (Cx26) gap junctions to close. Here, we use cryoelectron microscopy (cryo-EM) to determine the structure of human Cx26 gap junctions under increasing levels of PCO. We show a correlation between the level of PCO and the size of the aperture of the pore, governed by the N-terminal helices that line the pore. This indicates that CO alone is sufficient to cause conformational changes in the protein. Analysis of the conformational states shows that movements at the N terminus are linked to both subunit rotation and flexing of the transmembrane helices.
External linksStructure / PubMed:35276081 / PubMed Central
MethodsEM (single particle)
Resolution1.9 - 2.9 Å
Structure data

EMDB-13935, PDB-7qeo:
human Connexin 26 at 55mm Hg PCO2, pH7.4: two masked subunits, class C
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-13937, PDB-7qeq:
human Connexin 26 dodecamer at 90mmHg PCO2, pH7.4
Method: EM (single particle) / Resolution: 1.9 Å

EMDB-13938, PDB-7qer:
human Connexin 26 dodecamer at 55mm Hg PCO2, pH7.4
Method: EM (single particle) / Resolution: 2.2 Å

EMDB-13939, PDB-7qes:
human Connexin 26 at 55mm Hg PCO2, pH7.4: two masked subunits, class A
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-13940, PDB-7qet:
human Connexin 26 dodecamer at 20mmHg PCO2, pH7.4
Method: EM (single particle) / Resolution: 2.1 Å

EMDB-13941, PDB-7qeu:
human Connexin 26 at 55mmHg PCO2, pH7.4: two masked subunits, class B
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-13942, PDB-7qev:
human Connexin 26 at 55mm Hg PCO2, pH7.4:two masked subunits, class D
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-13943, PDB-7qew:
human Connexin 26 class 2 hexamer at 90mmHg PCO2, pH7.4
Method: EM (single particle) / Resolution: 2.1 Å

EMDB-13944, PDB-7qey:
human Connexin 26 class 1 hexamer at 90mmHg PCO2, pH7.4
Method: EM (single particle) / Resolution: 2.0 Å

Chemicals

ChemComp-LMT:
DODECYL-BETA-D-MALTOSIDE / detergent*YM

ChemComp-PTY:
PHOSPHATIDYLETHANOLAMINE / phospholipid*YM

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Gap junction / Ion Channel / carbon dioxide sensitive

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