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Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy
The condensin protein complex compacts chromatin during mitosis using its DNA-loop extrusion activity. Previous studies proposed scrunching and loop-capture models as molecular mechanisms for the loop extrusion process, both of which assume the binding of double-strand (ds) DNA to the hinge domain f...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357123/ https://www.ncbi.nlm.nih.gov/pubmed/34329301 http://dx.doi.org/10.1371/journal.pcbi.1009265 |
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author | Koide, Hiroki Kodera, Noriyuki Bisht, Shveta Takada, Shoji Terakawa, Tsuyoshi |
author_facet | Koide, Hiroki Kodera, Noriyuki Bisht, Shveta Takada, Shoji Terakawa, Tsuyoshi |
author_sort | Koide, Hiroki |
collection | PubMed |
description | The condensin protein complex compacts chromatin during mitosis using its DNA-loop extrusion activity. Previous studies proposed scrunching and loop-capture models as molecular mechanisms for the loop extrusion process, both of which assume the binding of double-strand (ds) DNA to the hinge domain formed at the interface of the condensin subunits Smc2 and Smc4. However, how the hinge domain contacts dsDNA has remained unknown. Here, we conducted atomic force microscopy imaging of the budding yeast condensin holo-complex and used this data as basis for coarse-grained molecular dynamics simulations to model the hinge structure in a transient open conformation. We then simulated the dsDNA binding to open and closed hinge conformations, predicting that dsDNA binds to the outside surface when closed and to the outside and inside surfaces when open. Our simulations also suggested that the hinge can close around dsDNA bound to the inside surface. Based on these simulation results, we speculate that the conformational change of the hinge domain might be essential for the dsDNA binding regulation and play roles in condensin-mediated DNA-loop extrusion. |
format | Online Article Text |
id | pubmed-8357123 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-83571232021-08-12 Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy Koide, Hiroki Kodera, Noriyuki Bisht, Shveta Takada, Shoji Terakawa, Tsuyoshi PLoS Comput Biol Research Article The condensin protein complex compacts chromatin during mitosis using its DNA-loop extrusion activity. Previous studies proposed scrunching and loop-capture models as molecular mechanisms for the loop extrusion process, both of which assume the binding of double-strand (ds) DNA to the hinge domain formed at the interface of the condensin subunits Smc2 and Smc4. However, how the hinge domain contacts dsDNA has remained unknown. Here, we conducted atomic force microscopy imaging of the budding yeast condensin holo-complex and used this data as basis for coarse-grained molecular dynamics simulations to model the hinge structure in a transient open conformation. We then simulated the dsDNA binding to open and closed hinge conformations, predicting that dsDNA binds to the outside surface when closed and to the outside and inside surfaces when open. Our simulations also suggested that the hinge can close around dsDNA bound to the inside surface. Based on these simulation results, we speculate that the conformational change of the hinge domain might be essential for the dsDNA binding regulation and play roles in condensin-mediated DNA-loop extrusion. Public Library of Science 2021-07-30 /pmc/articles/PMC8357123/ /pubmed/34329301 http://dx.doi.org/10.1371/journal.pcbi.1009265 Text en © 2021 Koide et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Koide, Hiroki Kodera, Noriyuki Bisht, Shveta Takada, Shoji Terakawa, Tsuyoshi Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy |
title | Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy |
title_full | Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy |
title_fullStr | Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy |
title_full_unstemmed | Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy |
title_short | Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy |
title_sort | modeling of dna binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357123/ https://www.ncbi.nlm.nih.gov/pubmed/34329301 http://dx.doi.org/10.1371/journal.pcbi.1009265 |
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