How B-DNA Dynamics Decipher Sequence-Selective Protein Recognition.
DNA–protein recognition
PDB data mining
molecular dynamics
principal component analysis
structural analysis
Journal
Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R
Informations de publication
Date de publication:
06 09 2019
06 09 2019
Historique:
received:
13
05
2019
revised:
09
07
2019
accepted:
10
07
2019
pubmed:
22
7
2019
medline:
17
6
2020
entrez:
21
7
2019
Statut:
ppublish
Résumé
The rules governing sequence-specific DNA-protein recognition are under a long-standing debate regarding the prevalence of base versus shape readout mechanisms to explain sequence specificity and of the conformational selection versus induced fit binding paradigms to explain binding-related conformational changes in DNA. Using a combination of atomistic simulations on a subset of representative sequences and mesoscopic simulations at the protein-DNA interactome level, we demonstrate the prevalence of the shape readout model in determining sequence-specificity and of the conformational selection paradigm in defining the general mechanism for binding-related conformational changes in DNA. Our results suggest that the DNA uses a double mechanism to adapt its structure to the protein: it moves along the easiest deformation modes to approach the bioactive conformation, while final adjustments require localized rearrangements at the base-pair step and backbone level. Our study highlights the large impact of B-DNA dynamics in modulating DNA-protein binding.
Identifiants
pubmed: 31325439
pii: S0022-2836(19)30451-6
doi: 10.1016/j.jmb.2019.07.021
pii:
doi:
Substances chimiques
DNA, B-Form
0
DNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3845-3859Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.