DNA opening during transcription initiation by RNA polymerase II in atomic detail.
Journal
Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626
Informations de publication
Date de publication:
15 11 2022
15 11 2022
Historique:
received:
13
05
2022
revised:
01
09
2022
accepted:
07
10
2022
pubmed:
15
10
2022
medline:
22
11
2022
entrez:
14
10
2022
Statut:
ppublish
Résumé
RNA polymerase II (RNAP II) synthesizes RNA by reading the DNA code. During transcription initiation, RNAP II opens the double-stranded DNA to expose the DNA template to the active site. The molecular interactions driving and controlling DNA opening are not well understood. We used all-atom steered molecular dynamics simulations to derive a continuous pathway of DNA opening in human RNAP II, involving a 55 Å DNA strand displacement and a nearly 360° DNA helix rotation. To drive such large-scale transitions, we used a combination of RMSD-based collective variables, a newly designed rotational coordinate, and a path collective variable. The simulations reveal extensive interactions of the DNA with three conserved protein loops near the active site, namely with the rudder, fork loop 1, and fork loop 2. According to the simulations, DNA-protein interactions support DNA opening by a twofold mechanism; they catalyze DNA opening by attacking Watson-Crick hydrogen bonds, and they stabilize the open DNA bubble by the formation of a wide set of DNA-protein salt bridges.
Identifiants
pubmed: 36230000
pii: S0006-3495(22)00832-3
doi: 10.1016/j.bpj.2022.10.012
pmc: PMC9703100
pii:
doi:
Substances chimiques
DNA
9007-49-2
DNA-Directed RNA Polymerases
EC 2.7.7.6
RNA Polymerase II
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4299-4310Informations de copyright
Copyright © 2022 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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