5hew

Pentameric ligand-gated ion channel ELIC mutant T28D

spinqualitylabelsall models 5hew, resolution 4.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5hew is a 10 chain structure with sequence from Dickeya dadantii 3937. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 4.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function E0SJQ4_DICD3 Publication Abstract from PubMed Pentameric ligand-gated ion channels are activated by the binding of agonists to a site distant from the ion conduction path. These membrane proteins consist of distinct ligand-binding and pore domains that interact via an extended interface. Here, we have investigated the role of residues at this interface for channel activation to define critical interactions that couple conformational changes between the two structural units. By characterizing point mutants of the prokaryotic channels ELIC and GLIC by electrophysiology, X-ray crystallography and isothermal titration calorimetry, we have identified conserved residues that, upon mutation, apparently prevent activation but not ligand binding. The positions of nonactivating mutants cluster at a loop within the extracellular domain connecting beta-strands 6 and 7 and at a loop joining the pore-forming helix M2 with M3 where they contribute to a densely packed core of the protein. An ionic interaction in the extracellular domain between the turn connecting beta-strands 1 and 2 and a residue at the end of beta-strand 10 stabilizes a state of the receptor with high affinity for agonists, whereas contacts of this turn to a conserved proline residue in the M2-M3 loop appear to be less important than previously anticipated. When mapping residues with strong functional phenotype on different channel structures, mutual distances are closer in conducting than in nonconducting conformations, consistent with a potential role of contacts in the stabilization of the open state. Our study has revealed a pattern of interactions that are crucial for the relay of conformational changes from the extracellular domain to the pore region of prokaryotic pentameric ligand-gated ion channels. Due to the strong conservation of the interface, these results are relevant for the entire family. Signal Transduction at the Domain Interface of Prokaryotic Pentameric Ligand-Gated Ion Channels.,Bertozzi C, Zimmermann I, Engeler S, Hilf RJ, Dutzler R PLoS Biol. 2016 Mar 4;14(3):e1002393. doi: 10.1371/journal.pbio.1002393., eCollection 2016 Mar. PMID:26943937 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

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