Download MendeleyA locally closed conformation of a bacterial pentameric proton-gated ion channel.
Prevost, M.S., Sauguet, L., Nury, H., Van Renterghem, C., Huon, C., Poitevin, F., Baaden, M., Delarue, M., Corringer, P.J.(2012) Nat Struct Mol Biol 19: 642-649
- PubMed: 22580559
- DOI: https://doi.org/10.1038/nsmb.2307
- Primary Citation of Related Structures:
3TLS, 3TLT, 3TLU, 3TLV, 3TLW, 3UU3, 3UU4, 3UU5, 3UU6, 3UU8, 3UUB - PubMed Abstract:
Pentameric ligand-gated ion channels mediate signal transduction through conformational transitions between closed-pore and open-pore states. To stabilize a closed conformation of GLIC, a bacterial proton-gated homolog from Gloeobacter violaceus whose open structure is known, we separately generated either four cross-links or two single mutations. We found all six mutants to be in the same 'locally closed' conformation using X-ray crystallography, sharing most of the features of the open form but showing a locally closed pore as a result of a concerted bending of all of its M2 helices. The mutants adopt several variant conformations of the M2-M3 loop, and in all cases an interacting lipid that is observed in the open form disappears. A single cross-linked mutant is functional, according to electrophysiology, and the locally closed structure of this mutant indicates that it has an increased flexibility. Further cross-linking, accessibility and molecular dynamics data suggest that the locally closed form is a functionally relevant conformation that occurs during allosteric gating transitions.
Organizational Affiliation:
Institut Pasteur, Groupe R¨¦cepteurs-Canaux, Paris, France.
