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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.772486/full |
| _version_ | 1819037356525617152 |
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| author | Genki Shino Shoji Takada |
| author_facet | Genki Shino Shoji Takada |
| author_sort | Genki Shino |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T08:20:07Z |
| format | Article |
| id | doaj.art-55ce8823779b4fbc872a9e9ba21d8251 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-21T08:20:07Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-55ce8823779b4fbc872a9e9ba21d82512022-12-21T19:10:28ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-11-01810.3389/fmolb.2021.772486772486Modeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained ModelsGenki ShinoShoji TakadaRecently, 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.https://www.frontiersin.org/articles/10.3389/fmolb.2021.772486/fulltranscriptioneukaryotesprotein-DNA complexDNA openingmolecular dynamics simulation |
| spellingShingle | Genki Shino Shoji Takada Modeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained Models Frontiers in Molecular Biosciences transcription eukaryotes protein-DNA complex DNA opening molecular dynamics simulation |
| title | 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_short | 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 |
| topic | transcription eukaryotes protein-DNA complex DNA opening molecular dynamics simulation |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.772486/full |
| work_keys_str_mv | AT genkishino modelingdnaopeningintheeukaryotictranscriptioninitiationcomplexesviacoarsegrainedmodels AT shojitakada modelingdnaopeningintheeukaryotictranscriptioninitiationcomplexesviacoarsegrainedmodels |