3w9f

Crystal structure of the ankyrin repeat domain of chicken TRPV4 in complex with IP3

spinqualitylabelsall models 3w9f, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3w9f is a 4 chain structure with sequence from Gallus gallus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: I3P Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRPV4_CHICK Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:11081638). Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:11081638). Also activated by phorbol esters (PubMed:19864432). Channel activity seems to be regulated by a calmodulin-dependent mechanism (By similarity).[UniProtKB:Q9HBA0] Publication Abstract from PubMed Mutations in the ankyrin repeat domain (ARD) of TRPV4 are responsible for several channelopathies, including Charcot-Marie-Tooth disease type 2C and congenital distal and scapuloperoneal spinal muscular atrophy. However, the molecular pathogenesis mediated by these mutations remains elusive, mainly due to limited understanding of the TRPV4 ARD function. Here we show that phosphoinositide binding to the TRPV4 ARD leads to suppression of the channel activity. Among the phosphoinositides, phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) most potently binds to the TRPV4 ARD. The crystal structure of the TRPV4 ARD in complex with inositol-1,4,5-trisphosphate, the head-group of PI(4,5)P2, and the molecular-dynamics simulations revealed the PI(4,5)P2-binding amino-acid residues. The TRPV4 channel activities were increased by titration or hydrolysis of membrane PI(4,5)P2. Notably, disease-associated TRPV4 mutations that cause a gain-of-function phenotype abolished PI(4,5)P2 binding and PI(4,5)P2 sensitivity. These findings identify TRPV4 ARD as a lipid-binding domain in which interactions with PI(4,5)P2 normalize the channel activity in TRPV4. TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2.,Takahashi N, Hamada-Nakahara S, Itoh Y, Takemura K, Shimada A, Ueda Y, Kitamata M, Matsuoka R, Hanawa-Suetsugu K, Senju Y, Mori MX, Kiyonaka S, Kohda D, Kitao A, Mori Y, Suetsugu S Nat Commun. 2014 Sep 26;5:4994. doi: 10.1038/ncomms5994. PMID:25256292 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

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