6TIR

NOE based model of hVDAC-1 bound to beta-NADH in detergent micelles

6TIR の概要

• エントリーDOI: 10.2210/pdb6tir/pdb
• NMR情報: BMRB: 34457
• 分子名称: Voltage-dependent anion-selective channel protein 1, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE (2 entities in total)
• 機能のキーワード: beta-barrel membrane protein complex, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32544.10

構造登録者

Boehm, R.,Hiller, S.,Wagner, G. (登録日: 2019-11-22, 公開日: 2019-12-04, 最終更新日: 2024-05-15)

主引用文献

Bohm, R.,Amodeo, G.F.,Murlidaran, S.,Chavali, S.,Wagner, G.,Winterhalter, M.,Brannigan, G.,Hiller, S.
The Structural Basis for Low Conductance in the Membrane Protein VDAC upon beta-NADH Binding and Voltage Gating.
Structure, 28:206-214.e4, 2020

PubMed Abstract: The voltage-dependent anion channel (VDAC) forms the primary diffusion pore of the outer mitochondrial membrane. In its apo form, VDAC adopts an open conformation with high conductance. States of lower conductance can be induced by ligand binding or the application of voltage. Here, we clarify at the atomic level how β-NADH binding leads to a low-conductance state and characterize the role of the VDAC N-terminal helix in voltage gating. A high-resolution NMR structure of human VDAC-1 with bound NADH, combined with molecular dynamics simulation show that β-NADH binding reduces the pore conductance sterically without triggering a structural change. Electrophysiology recordings of crosslinked protein variants and NMR relaxation experiments probing different time scales show that increased helix dynamics is present in the open state and that motions of the N-terminal helices are involved in the VDAC voltage gating mechanism.

PubMed: 31862297
DOI: 10.1016/j.str.2019.11.015

実験手法

SOLUTION NMR