4LMK

GLIC Liganded-closed-channel Conformation, Mutant Y27'A

Summary for 4LMK

• Entry DOI: 10.2210/pdb4lmk/pdb
• Related: 4LMJ 4LML
• Descriptor: Proton-gated ion channel, CHLORIDE ION, DODECYL-BETA-D-MALTOSIDE, ... (4 entities in total)
• Functional Keywords: pentameric ligand-gated ion channel, membrane protein, prokaryotic cys-loop receptor, 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: 182166.39

Authors

Grosman, C.,Gonzalez-Gutierrez, G. (deposition date: 2013-07-10, release date: 2013-10-30, Last modification date: 2023-09-20)

Primary citation

Gonzalez-Gutierrez, G.,Cuello, L.G.,Nair, S.K.,Grosman, C.
Gating of the proton-gated ion channel from Gloeobacter violaceus at pH 4 as revealed by X-ray crystallography.
Proc.Natl.Acad.Sci.USA, 110:18716-18721, 2013

PubMed Abstract: Cryoelectron microscopy and X-ray crystallography have recently been used to generate structural models that likely represent the unliganded closed-channel conformation and the fully liganded open-channel conformation of different members of the nicotinic-receptor superfamily. To characterize the structure of the closed-channel conformation in its liganded state, we identified a number of positions in the loop between transmembrane segments 2 (M2) and 3 (M3) of a proton-gated ortholog from the bacterium Gloeobacter violaceus (GLIC) where mutations to alanine reduce the liganded-gating equilibrium constant, and solved the crystal structures of two such mutants (T25'A and Y27'A) at pH ~4.0. At the level of backbone atoms, the liganded closed-channel model presented here differs from the liganded open-channel structure of GLIC in the pre-M1 linker, the M3-M4 loop, and much more prominently, in the extracellular half of the pore lining, where the more pronounced tilt of the closed-channel M2 α-helices toward the pore's long axis narrows the permeation pathway. On the other hand, no differences between the liganded closed-channel and open-channel models could be detected at the level of the extracellular domain, where conformational changes are expected to underlie the low-to-high proton-affinity switch that drives gating of proton-bound channels. Thus, the liganded closed-channel model is nearly indistinguishable from the recently described "locally closed" structure. However, because cross-linking strategies (which could have stabilized unstable conformations) and mutations involving ionizable side chains (which could have affected proton-gated channel activation) were purposely avoided, we favor the notion that this structure represents one of the end states of liganded gating rather than an unstable intermediate.

PubMed: 24167270
DOI: 10.1073/pnas.1313156110

Experimental method

X-RAY DIFFRACTION (3.22 Å)