- PDB-9cuj: Structure of human full-length derived TRPV6 channel in apo open state -
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基本情報
登録情報
データベース: PDB / ID: 9cuj
タイトル
Structure of human full-length derived TRPV6 channel in apo open state
要素
Transient receptor potential cation channel subfamily V member 6
キーワード
MEMBRANE PROTEIN / transient receptor potential V family member 6 / TRP / channel / TRPV6 / TRP channels / derived
機能・相同性
機能・相同性情報
parathyroid hormone secretion / regulation of calcium ion-dependent exocytosis / TRP channels / calcium ion import across plasma membrane / calcium ion homeostasis / calcium channel complex / calcium ion transmembrane transport / calcium channel activity / response to calcium ion / calcium ion transport ...parathyroid hormone secretion / regulation of calcium ion-dependent exocytosis / TRP channels / calcium ion import across plasma membrane / calcium ion homeostasis / calcium channel complex / calcium ion transmembrane transport / calcium channel activity / response to calcium ion / calcium ion transport / calmodulin binding / metal ion binding / identical protein binding / plasma membrane 類似検索 - 分子機能
Transient receptor potential cation channel subfamily V member 6 / Transient receptor potential cation channel subfamily V member 5/6 / Transient receptor potential cation channel subfamily V / Ankyrin repeat / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily ...Transient receptor potential cation channel subfamily V member 6 / Transient receptor potential cation channel subfamily V member 5/6 / Transient receptor potential cation channel subfamily V / Ankyrin repeat / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily / Ion transport domain / Ion transport protein 類似検索 - ドメイン・相同性
1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / Chem-POV / CHOLESTEROL HEMISUCCINATE / Transient receptor potential cation channel subfamily V member 6 類似検索 - 構成要素
National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS)
R01 AR078814
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
R01 CA206573
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01 NS083660
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01 NS107253
米国
German Research Foundation (DFG)
464295817
ドイツ
引用
ジャーナル: Structure / 年: 2025 タイトル: Structure-function analyses of human TRPV6 ancestral and derived haplotypes. 著者: Arthur Neuberger / Alexey Shalygin / Yury A Trofimov / Irina I Veretenenko / Kirill D Nadezhdin / Nikolay A Krylov / Thomas Gudermann / Roman G Efremov / Vladimir Chubanov / Alexander I Sobolevsky / 要旨: 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 ...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.