3UU8: The Glic Pentameric Ligand-Gated Ion Channel Loop2-24' Mutant Reduced In Solution

Citation:
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.
PDB ID: 3UU8Download
MMDB ID: 99681
PDB Deposition Date: 2011/11/28
Updated in MMDB: 2012/06
Experimental Method:
x-ray diffraction
Resolution: 3.25  Å
Source Organism:
Similar Structures:
Biological Unit for 3UU8: pentameric; determined by author and by software (PISA)
Molecular Components in 3UU8
Label Count Molecule
Proteins (5 molecules)
5
Glr4197 Protein(Gene symbol: glr4197)
Molecule annotation
Chemicals (27 molecules)
1
15
2
5
3
6
4
1
* Click molecule labels to explore molecular sequence information.

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