8tf2 | pdb_00008tf2

Wildtype rabbit TRPV5 into nanodiscs in Apo state

spinqualitylabelsall models 8tf2, resolution 2.57Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8tf2 is a 4 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.57Å Ligands: CPL, ERG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRPV5_RABIT Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:12574114). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (By similarity). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (PubMed:12574114).[UniProtKB:P69744][UniProtKB:Q9NQA5] Publication Abstract from PubMed The calcium-selective TRPV5 channel activated by phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] is involved in calcium homeostasis. Recently, cryoelectron microscopy (cryo-EM) provided molecular details of TRPV5 modulation by exogenous and endogenous molecules. However, the details of TRPV5 inhibition by the antifungal agent econazole (ECN) remain elusive due to the low resolution of the currently available structure. In this study, we employ cryo-EM to comprehensively examine how the ECN inhibits TRPV5. By combining our structural findings with site-directed mutagenesis, calcium measurements, electrophysiology, and molecular dynamics simulations, we determined that residues F472 and L475 on the S4 helix, along with residue W495 on the S5 helix, collectively constitute the ECN-binding site. Additionally, the structure of TRPV5 in the presence of ECN and PI(4,5)P(2), which does not show the bound activator, reveals a potential inhibition mechanism in which ECN competes with PI(4,5)P(2), preventing the latter from binding, and ultimately pore closure. Structural mechanism of TRPV5 inhibition by econazole.,De Jesus-Perez JJ, Gabrielle M, Raheem S, Fluck EC, Rohacs T, Moiseenkova-Bell VY Structure. 2023 Dec 19:S0969-2126(23)00438-0. doi: 10.1016/j.str.2023.11.012. PMID:38141613 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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