3TLS

The GLIC pentameric Ligand-Gated Ion Channel E19'P mutant in a locally-closed conformation (LC2 subtype)

Summary for 3TLS

• Entry DOI: 10.2210/pdb3tls/pdb
• Related: 3TLT 3TLU 3TLV 3TLW
• Descriptor: Glr4197 protein, CHLORIDE ION, DODECYL-BETA-D-MALTOSIDE, ... (4 entities in total)
• Functional Keywords: cys-loop receptor family, membrane protein, transport protein
• Biological source: Gloeobacter violaceus
• Cellular location: Cell inner membrane; Multi-pass membrane protein (Probable): Q7NDN8
• Total number of polymer chains: 5
• Total formula weight: 183418.07

Authors

Sauguet, L.,Nury, H.,Corringer, P.J.,Delarue, M. (deposition date: 2011-08-30, release date: 2012-05-16, Last modification date: 2024-02-28)

Primary citation

Prevost, M.S.,Sauguet, L.,Nury, H.,Van Renterghem, C.,Huon, C.,Poitevin, F.,Baaden, M.,Delarue, M.,Corringer, P.J.
A locally closed conformation of a bacterial pentameric proton-gated ion channel.
Nat.Struct.Mol.Biol., 19:642-649, 2012

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.

PubMed: 22580559
DOI: 10.1038/nsmb.2307

Experimental method

X-RAY DIFFRACTION (3.2 Å)