7rys | pdb_00007rys

SthK R120A Open State 2

spinqualitylabelsall models 7rys, resolution 3.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7rys is a 4 chain structure with sequence from Spirochaeta thermophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.7Å Ligands: CMP, PGW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G0GA88_SPITZ Publication Abstract from PubMed Understanding how ion channels gate is important for elucidating their physiological roles and targeting them in pathophysiological states. Here, we used SthK, a cyclic nucleotide-modulated channel from Spirochaeta thermophila, to define a ligand-gating trajectory that includes multiple on-pathway intermediates. cAMP is a poor partial agonist for SthK and depolarization increases SthK activity. Tuning the energy landscape by gain-of-function mutations in the voltage sensor domain (VSD) allowed us to capture multiple intermediates along the ligand-activation pathway, highlighting the allosteric linkage between VSD, cyclic nucleotide-binding (CNBD) and pore domains. Small, lateral displacements of the VSD S4 segment were necessary to open the intracellular gate, pointing to an inhibitory VSD at rest. We propose that in wild-type SthK, depolarization leads to such VSD displacements resulting in release of inhibition. In summary, we report conformational transitions along the activation pathway that reveal allosteric couplings between key sites integrating to open the intracellular gate. Gating intermediates reveal inhibitory role of the voltage sensor in a cyclic nucleotide-modulated ion channel.,Gao X, Schmidpeter PAM, Berka V, Durham RJ, Fan C, Jayaraman V, Nimigean CM Nat Commun. 2022 Nov 14;13(1):6919. doi: 10.1038/s41467-022-34673-z. PMID:36376326 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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