Copper coordination states affect the flexibility of copper Metallochaperone Atox1: Insights from molecular dynamics simulations.
Atox1
copper-binding
molecular dynamics
molecular simulations
protein flexibility
Journal
Protein science : a publication of the Protein Society
ISSN: 1469-896X
Titre abrégé: Protein Sci
Pays: United States
ID NLM: 9211750
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
15
09
2022
received:
19
05
2022
accepted:
04
10
2022
pubmed:
9
10
2022
medline:
2
12
2022
entrez:
8
10
2022
Statut:
ppublish
Résumé
Copper is an essential element in nature but in excess, it is toxic to the living cell. The human metallochaperone Atox1 participates in copper homeostasis and is responsible for copper transmission. In a previous multiscale simulation study, we noticed a change in the coordination state of the Cu(I) ion, from 4 bound cysteine residues to 3, in agreement with earlier studies. Here, we perform and analyze classical molecular dynamic simulations of various coordination states: 2, 3, and 4. The main observation is an increase in protein flexibility as a result of a decrease in the coordination state. In addition, we identified several populated conformations that correlate well with double electron-electron resonance distance distributions or an X-ray structure of Cu(I)-bound Atox1. We suggest that the increased flexibility might benefit the process of ion transmission between interacting proteins. Further experiments can scrutinize this hypothesis and shed additional light on the mechanism of action of Atox1.
Identifiants
pubmed: 36208051
doi: 10.1002/pro.4464
pmc: PMC9667823
doi:
Substances chimiques
Metallochaperones
0
Copper
789U1901C5
Copper Transport Proteins
0
Cation Transport Proteins
0
Molecular Chaperones
0
ATOX1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e4464Informations de copyright
© 2022 The Protein Society.
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