9CUI

Structure of human full-length ancestral TRPV6 channel in Calmodulin-bound state

9CUI の概要

• エントリーDOI: 10.2210/pdb9cui/pdb
• EMDBエントリー: 45934
• 分子名称: Transient receptor potential cation channel subfamily V member 6, Calmodulin-1, CHOLESTEROL HEMISUCCINATE, ... (6 entities in total)
• 機能のキーワード: transient receptor potential v family member 6, trp, channel, trpv6, trp channels, membrane protein, ancestral, calmodulin
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 405921.28

構造登録者

Neuberger, A.,Nadezhdin, K.D.,Sobolevsky, A.I. (登録日: 2024-07-26, 公開日: 2024-11-13, 最終更新日: 2025-06-04)

主引用文献

Neuberger, A.,Shalygin, A.,Trofimov, Y.A.,Veretenenko, I.I.,Nadezhdin, K.D.,Krylov, N.A.,Gudermann, T.,Efremov, R.G.,Chubanov, V.,Sobolevsky, A.I.
Structure-function analyses of human TRPV6 ancestral and derived haplotypes.
Structure, 33:91-103.e5, 2025

PubMed Abstract: TRPV6 is a Ca 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 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.

PubMed: 39500315
DOI: 10.1016/j.str.2024.10.018

実験手法

ELECTRON MICROSCOPY (3.42 Å)