Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structures of wild-type and a constitutively closed mutant of connexin26 shed light on channel regulation by CO.
Journal, issue, pages	Elife, Vol. 13, Year 2024
Publish date	Jun 3, 2024
Authors	Deborah H Brotherton / Sarbjit Nijjar / Christos G Savva / Nicholas Dale / Alexander David Cameron /
PubMed Abstract	Connexins allow intercellular communication by forming gap junction channels (GJCs) between juxtaposed cells. Connexin26 (Cx26) can be regulated directly by CO. This is proposed to be mediated ...Connexins allow intercellular communication by forming gap junction channels (GJCs) between juxtaposed cells. Connexin26 (Cx26) can be regulated directly by CO. This is proposed to be mediated through carbamylation of K125. We show that mutating K125 to glutamate, mimicking the negative charge of carbamylation, causes Cx26 GJCs to be constitutively closed. Through cryo-EM we observe that the K125E mutation pushes a conformational equilibrium towards the channel having a constricted pore entrance, similar to effects seen on raising the partial pressure of CO. In previous structures of connexins, the cytoplasmic loop, important in regulation and where K125 is located, is disordered. Through further cryo-EM studies we trap distinct states of Cx26 and observe density for the cytoplasmic loop. The interplay between the position of this loop, the conformations of the transmembrane helices and the position of the N-terminal helix, which controls the aperture to the pore, provides a mechanism for regulation.
External links	Elife / PubMed:38829031 / PubMed Central
Methods	EM (single particle)
Resolution	2.1 - 4.9 Å
Structure data	18290 8q9z EMDB-18290, PDB-8q9z: Cryo-EM structure of Cx26 gap junction K125E mutant in bicarbonate buffer (classification on hemichannel) Method: EM (single particle) / Resolution: 2.4 Å 18291 8qa0 EMDB-18291, PDB-8qa0: Cryo-EM structure of Cx26 solubilised in LMNG - hemichannel classification - NConst conformation Method: EM (single particle) / Resolution: 2.3 Å 18292 8qa1 EMDB-18292, PDB-8qa1: Cryo-EM structure of Cx26 solubilised in LMNG - Hemichannel classification NFlex conformation Method: EM (single particle) / Resolution: 2.3 Å 18293 8qa2 EMDB-18293, PDB-8qa2: Cryo-EM structure of Cx26 solubilised in LMNG: classification on subunit A; Nconst-mon conformation Method: EM (single particle) / Resolution: 2.3 Å 18294 8qa3 EMDB-18294, PDB-8qa3: Cryo-EM structure of Cx26 solubilised in LMNG: classification on subunit A; NFlex conformation Method: EM (single particle) / Resolution: 2.3 Å EMDB-18295: Cryo-EM reconstruction of Cx26 gap junction K125R mutant (D6 symmetry) Method: EM (single particle) / Resolution: 2.1 Å EMDB-18296: Cryo-EM reconstruction of Cx26 gap junction K125E mutant in HEPES buffer Method: EM (single particle) / Resolution: 4.3 Å EMDB-18297: Cryo-EM reconstruction of Cx26 gap junction WT in HEPES buffer Method: EM (single particle) / Resolution: 4.9 Å
Chemicals	ChemComp-LMT: DODECYL-BETA-D-MALTOSIDE / detergentYM ChemComp-PTY: PHOSPHATIDYLETHANOLAMINE / phospholipidYM ChemComp-HOH: WATER
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / Gap junction Large Pore Channel Carbon dioxide sensitive