Experimental diagnostic of sequence-variant dynamic perturbations revealed by broadband dielectric spectroscopy.
B-subunit toxin pentamers
broadband dielectric spectroscopy
dynamics faults
multiple scale dynamics
nanoscale
protein unfolding
sequence variants
slow protein dynamics
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
02 12 2021
02 12 2021
Historique:
received:
14
12
2020
revised:
23
03
2021
accepted:
07
05
2021
pubmed:
30
5
2021
medline:
22
3
2022
entrez:
29
5
2021
Statut:
ppublish
Résumé
Genetic diversity leads to protein robustness, adaptability, and failure. Some sequence variants are structurally robust but functionally disturbed because mutations bring the protein onto unfolding/refolding routes resulting in misfolding diseases (e.g., Parkinson). We assume dynamic perturbations introduced by mutations foster the alternative unfolding routes and test this possibility by comparing the unfolding dynamics of the heat-labile enterotoxin B pentamers and the cholera toxin B pentamers, two pentamers structurally and functionally related and robust to 17 sequence variations. The B-subunit thermal unfolding dynamics are monitored by broadband dielectric spectroscopy in nanoconfined and weakly hydrated conditions. Distinct dielectric signals reveal the different B-subunits unfolding dynamics. Combined with network analyses, the experiments pinpoint the role of three mutations A1T, E7D, and E102A, in diverting LTB
Identifiants
pubmed: 34051139
pii: S0969-2126(21)00163-5
doi: 10.1016/j.str.2021.05.005
pii:
doi:
Substances chimiques
Enterotoxins
0
Cholera Toxin
9012-63-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1419-1429.e3Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.