Modeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained Models

Recently, the molecular mechanisms of transcription initiation have been intensively studied. Especially, the cryo-electron microscopy revealed atomic structure details in key states in the eukaryotic transcription initiation. Yet, the dynamic processes of the promoter DNA opening in the pre-initiat...

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Autores principales:	Genki Shino, Shoji Takada
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	transcription eukaryotes protein-DNA complex DNA opening molecular dynamics simulation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/55ce8823779b4fbc872a9e9ba21d8251
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spelling	oai:doaj.org-article:55ce8823779b4fbc872a9e9ba21d82512021-11-15T06:45:01ZModeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained Models2296-889X10.3389/fmolb.2021.772486https://doaj.org/article/55ce8823779b4fbc872a9e9ba21d82512021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.772486/fullhttps://doaj.org/toc/2296-889XRecently, the molecular mechanisms of transcription initiation have been intensively studied. Especially, the cryo-electron microscopy revealed atomic structure details in key states in the eukaryotic transcription initiation. Yet, the dynamic processes of the promoter DNA opening in the pre-initiation complex remain obscured. In this study, based on the three cryo-electron microscopic yeast structures for the closed, open, and initially transcribing complexes, we performed multiscale molecular dynamics (MD) simulations to model structures and dynamic processes of DNA opening. Combining coarse-grained and all-atom MD simulations, we first obtained the atomic model for the DNA bubble in the open complexes. Then, in the MD simulation from the open to the initially transcribing complexes, we found a previously unidentified intermediate state which is formed by the bottleneck in the fork loop 1 of Pol II: The loop opening triggered the escape from the intermediate, serving as a gatekeeper of the promoter DNA opening. In the initially transcribing complex, the non-template DNA strand passes a groove made of the protrusion, the lobe, and the fork of Rpb2 subunit of Pol II, in which several positively charged and highly conserved residues exhibit key interactions to the non-template DNA strand. The back-mapped all-atom models provided further insights on atomistic interactions such as hydrogen bonding and can be used for future simulations.Genki ShinoShoji TakadaFrontiers Media S.A.articletranscriptioneukaryotesprotein-DNA complexDNA openingmolecular dynamics simulationBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	transcription eukaryotes protein-DNA complex DNA opening molecular dynamics simulation Biology (General) QH301-705.5
spellingShingle	transcription eukaryotes protein-DNA complex DNA opening molecular dynamics simulation Biology (General) QH301-705.5 Genki Shino Shoji Takada Modeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained Models
description	Recently, the molecular mechanisms of transcription initiation have been intensively studied. Especially, the cryo-electron microscopy revealed atomic structure details in key states in the eukaryotic transcription initiation. Yet, the dynamic processes of the promoter DNA opening in the pre-initiation complex remain obscured. In this study, based on the three cryo-electron microscopic yeast structures for the closed, open, and initially transcribing complexes, we performed multiscale molecular dynamics (MD) simulations to model structures and dynamic processes of DNA opening. Combining coarse-grained and all-atom MD simulations, we first obtained the atomic model for the DNA bubble in the open complexes. Then, in the MD simulation from the open to the initially transcribing complexes, we found a previously unidentified intermediate state which is formed by the bottleneck in the fork loop 1 of Pol II: The loop opening triggered the escape from the intermediate, serving as a gatekeeper of the promoter DNA opening. In the initially transcribing complex, the non-template DNA strand passes a groove made of the protrusion, the lobe, and the fork of Rpb2 subunit of Pol II, in which several positively charged and highly conserved residues exhibit key interactions to the non-template DNA strand. The back-mapped all-atom models provided further insights on atomistic interactions such as hydrogen bonding and can be used for future simulations.
format	article
author	Genki Shino Shoji Takada
author_facet	Genki Shino Shoji Takada
author_sort	Genki Shino
title	Modeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained Models
title_short	Modeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained Models
title_full	Modeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained Models
title_fullStr	Modeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained Models
title_full_unstemmed	Modeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained Models
title_sort	modeling dna opening in the eukaryotic transcription initiation complexes via coarse-grained models
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/55ce8823779b4fbc872a9e9ba21d8251
work_keys_str_mv	AT genkishino modelingdnaopeningintheeukaryotictranscriptioninitiationcomplexesviacoarsegrainedmodels AT shojitakada modelingdnaopeningintheeukaryotictranscriptioninitiationcomplexesviacoarsegrainedmodels
_version_	1718428552719761408

Modeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained Models

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