The N-Terminal Segment of the Voltage-Dependent Anion Channel: A Possible Membrane-Bound Intermediate in Pore Unbinding.
N-terminal helix
chemical shift perturbations
membrane binding
potential of mean force
voltage-dependent anion channel
Journal
Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R
Informations de publication
Date de publication:
18 01 2019
18 01 2019
Historique:
received:
26
06
2018
revised:
11
09
2018
accepted:
26
09
2018
pubmed:
20
10
2018
medline:
3
3
2020
entrez:
20
10
2018
Statut:
ppublish
Résumé
The voltage-dependent anion channel (VDAC) resides in the outer mitochondrial membrane and can adopt a closed or open configuration, most likely depending on whether the N-terminal segment (NTS) occupies the pore or protrudes into the cytoplasm. In this study, we calculate the free energy of releasing the NTS from the pore using molecular dynamics simulation. This is complicated by the flexible nature of the NTS, in particular its disordered structure in aqueous solution compared to the pore lumen. We carried out potential of mean force calculations using enhanced sampling or conformational restraints to address the conformational sampling problem. For the binding to the VDAC pore, two systems were considered, featuring either the native VDAC system or a modified system where the NTS is detached from the pore, that is, noncovalently bound in the pore lumen. The calculated free energies required to translocate the NTS from the pore into the solvent moiety are 83.8 or 74.3 kJ mol
Identifiants
pubmed: 30339869
pii: S0022-2836(18)30694-6
doi: 10.1016/j.jmb.2018.09.015
pii:
doi:
Substances chimiques
Peptides
0
Phospholipids
0
Voltage-Dependent Anion Channels
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
223-243Informations de copyright
Copyright © 2018 Elsevier Ltd. All rights reserved.