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:	Hiroki Koide, Noriyuki Kodera, Shveta Bisht, Shoji Takada, Tsuyoshi Terakawa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/edfbe74147e84b2c96ba1d9f79984d3b
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spelling	oai:doaj.org-article:edfbe74147e84b2c96ba1d9f79984d3b2021-12-02T19:57:20ZModeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy.1553-734X1553-735810.1371/journal.pcbi.1009265https://doaj.org/article/edfbe74147e84b2c96ba1d9f79984d3b2021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009265https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The 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.Hiroki KoideNoriyuki KoderaShveta BishtShoji TakadaTsuyoshi TerakawaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 7, p e1009265 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Hiroki Koide Noriyuki Kodera Shveta Bisht Shoji Takada Tsuyoshi Terakawa Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy.
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	article
author	Hiroki Koide Noriyuki Kodera Shveta Bisht Shoji Takada Tsuyoshi Terakawa
author_facet	Hiroki Koide Noriyuki Kodera Shveta Bisht Shoji Takada Tsuyoshi Terakawa
author_sort	Hiroki Koide
title	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_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_sort	modeling of dna binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/edfbe74147e84b2c96ba1d9f79984d3b
work_keys_str_mv	AT hirokikoide modelingofdnabindingtothecondensinhingedomainusingmoleculardynamicssimulationsguidedbyatomicforcemicroscopy AT noriyukikodera modelingofdnabindingtothecondensinhingedomainusingmoleculardynamicssimulationsguidedbyatomicforcemicroscopy AT shvetabisht modelingofdnabindingtothecondensinhingedomainusingmoleculardynamicssimulationsguidedbyatomicforcemicroscopy AT shojitakada modelingofdnabindingtothecondensinhingedomainusingmoleculardynamicssimulationsguidedbyatomicforcemicroscopy AT tsuyoshiterakawa modelingofdnabindingtothecondensinhingedomainusingmoleculardynamicssimulationsguidedbyatomicforcemicroscopy
_version_	1718375876544954368

Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy.

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