7JMC

Sheep Connexin-50 at 2.5 angstroms resolution, Lipid Class 3

Summary for 7JMC

• Entry DOI: 10.2210/pdb7jmc/pdb
• EMDB information: 22391
• Descriptor: Gap junction alpha-8 protein, 1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE (3 entities in total)
• Functional Keywords: connexin, gap junction, lipid, nanodisc, membrane protein
• Biological source: Ovis aries (Sheep)
• Total number of polymer chains: 12
• Total formula weight: 688224.06

Authors

Flores, J.A.,Haddad, B.G.,Dolan, K.D.,Myers, J.B.,Yoshioka, C.C.,Copperman, J.,Zuckerman, D.M.,Reichow, S.L. (deposition date: 2020-07-31, release date: 2020-09-09, Last modification date: 2024-10-23)

Primary citation

Flores, J.A.,Haddad, B.G.,Dolan, K.A.,Myers, J.B.,Yoshioka, C.C.,Copperman, J.,Zuckerman, D.M.,Reichow, S.L.
Connexin-46/50 in a dynamic lipid environment resolved by CryoEM at 1.9 angstrom.
Nat Commun, 11:4331-4331, 2020

PubMed Abstract: Gap junctions establish direct pathways for cells to transfer metabolic and electrical messages. The local lipid environment is known to affect the structure, stability and intercellular channel activity of gap junctions; however, the molecular basis for these effects remains unknown. Here, we incorporate native connexin-46/50 (Cx46/50) intercellular channels into a dual lipid nanodisc system, mimicking a native cell-to-cell junction. Structural characterization by CryoEM reveals a lipid-induced stabilization to the channel, resulting in a 3D reconstruction at 1.9 Å resolution. Together with all-atom molecular dynamics simulations, it is shown that Cx46/50 in turn imparts long-range stabilization to the dynamic local lipid environment that is specific to the extracellular lipid leaflet. In addition, ~400 water molecules are resolved in the CryoEM map, localized throughout the intercellular permeation pathway and contributing to the channel architecture. These results illustrate how the aqueous-lipid environment is integrated with the architectural stability, structure and function of gap junction communication channels.

PubMed: 32859914
DOI: 10.1038/s41467-020-18120-5

Experimental method

ELECTRON MICROSCOPY (2.5 Å)