5svm

Crystal structure of the ATP-gated human P2X3 ion channel bound to agonist 2-methylthio-ATP in the desensitized state

spinqualitylabelsall models 5svm, resolution 3.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5svm is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.093Å Ligands: 6AT, ATP, EDO, NA, NAG, TRS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function P2RX3_HUMAN Receptor for ATP that acts as a ligand-gated ion channel. Publication Abstract from PubMed P2X receptors are trimeric, non-selective cation channels activated by ATP that have important roles in the cardiovascular, neuronal and immune systems. Despite their central function in human physiology and although they are potential targets of therapeutic agents, there are no structures of human P2X receptors. The mechanisms of receptor desensitization and ion permeation, principles of antagonism, and complete structures of the pore-forming transmembrane domains of these receptors remain unclear. Here we report X-ray crystal structures of the human P2X3 receptor in apo/resting, agonist-bound/open-pore, agonist-bound/closed-pore/desensitized and antagonist-bound/closed states. The open state structure harbours an intracellular motif we term the 'cytoplasmic cap', which stabilizes the open state of the ion channel pore and creates lateral, phospholipid-lined cytoplasmic fenestrations for water and ion egress. The competitive antagonists TNP-ATP and A-317491 stabilize the apo/resting state and reveal the interactions responsible for competitive inhibition. These structures illuminate the conformational rearrangements that underlie P2X receptor gating and provide a foundation for the development of new pharmacological agents. X-ray structures define human P2X3 receptor gating cycle and antagonist action.,Mansoor SE, Lu W, Oosterheert W, Shekhar M, Tajkhorshid E, Gouaux E Nature. 2016 Sep 14. doi: 10.1038/nature19367. PMID:27626375 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA