9cuh

Structure of human full-length ancestral TRPV6 channel in apo open state

spinqualitylabelsall models 9cuh, resolution 3.03Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9cuh is a 4 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: Electron Microscopy, Resolution 3.03Å Ligands: CA, PCW, POV, Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed TRPV6 is a Ca(2+) selective channel that mediates calcium uptake in the gut and contributes to the development and progression of human cancers. TRPV6 is represented by the ancestral and derived haplotypes that differ by three non-synonymous polymorphisms, located in the N-terminal ankyrin repeat domain (C157R), S1-S2 extracellular loop (M378V), and C-terminus (M681T). The ancestral and derived haplotypes were proposed to serve as genomic factors causing a different outcome for cancer patients of African ancestry. We solved cryoelectron microscopy (cryo-EM) structures of ancestral and derived TRPV6 in the open and calmodulin (CaM)-bound inactivated states. Neither state shows substantial structural differences caused by the non-synonymous polymorphisms. Functional properties assessed by electrophysiological recordings and Ca(2+) uptake measurements, and water and ion permeation evaluated by molecular modeling also appear similar between the haplotypes. Therefore, ancestral and derived TRPV6 have similar structure and function, implying that other factors are responsible for the differences in susceptibility to cancer. Structure-function analyses of human TRPV6 ancestral and derived haplotypes.,Neuberger A, Shalygin A, Trofimov YA, Veretenenko II, Nadezhdin KD, Krylov NA, Gudermann T, Efremov RG, Chubanov V, Sobolevsky AI Structure. 2024 Oct 28:S0969-2126(24)00453-2. doi: 10.1016/j.str.2024.10.018. PMID:39500315 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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