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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...

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Autores principales: Koide, Hiroki, Kodera, Noriyuki, Bisht, Shveta, Takada, Shoji, Terakawa, Tsuyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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