6ave | pdb_00006ave

Structure of an acid sensing ion channel in a resting state at high pH

spinqualitylabelsall models 6ave, resolution 3.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ave is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAG Related: 5wku, 5wkv, 5wkx, 5wky Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ASIC1_CHICK] Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride (By similarity). Publication Abstract from PubMed Acid-sensing ion channels (ASICs) are trimeric, proton-gated and sodium-selective members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout vertebrate central and peripheral nervous systems. Gating of ASICs occurs on a millisecond time scale and the mechanism involves three conformational states: high pH resting, low pH open and low pH desensitized. Existing X-ray structures of ASIC1a describe the conformations of the open and desensitized states, but the structure of the high pH resting state and detailed mechanisms of the activation and desensitization of the channel have remained elusive. Here we present structures of the high pH resting state of homotrimeric chicken (Gallus gallus) ASIC1a, determined by X-ray crystallography and single particle cryo-electron microscopy, and present a comprehensive molecular mechanism for proton-dependent gating in ASICs. In the resting state, the position of the thumb domain is further from the three-fold molecular axis, thereby expanding the 'acidic pocket' in comparison to the open and desensitized states. Activation therefore involves 'closure' of the thumb into the acidic pocket, expansion of the lower palm domain and an iris-like opening of the channel gate. Furthermore, we demonstrate how the beta11-beta12 linkers that demarcate the upper and lower palm domains serve as a molecular 'clutch', and undergo a simple rearrangement to permit rapid desensitization. Gating mechanisms of acid-sensing ion channels.,Yoder N, Yoshioka C, Gouaux E Nature. 2018 Mar 15;555(7696):397-401. doi: 10.1038/nature25782. Epub 2018 Mar 7. PMID:29513651 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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