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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2021-07-01
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Online Access: | https://doi.org/10.1371/journal.pcbi.1009265 |
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doaj-edfbe74147e84b2c96ba1d9f79984d3b2021-08-16T04:32:08ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-07-01177e100926510.1371/journal.pcbi.1009265Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy.Hiroki KoideNoriyuki KoderaShveta BishtShoji TakadaTsuyoshi TerakawaThe 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.https://doi.org/10.1371/journal.pcbi.1009265 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hiroki Koide Noriyuki Kodera Shveta Bisht Shoji Takada Tsuyoshi Terakawa |
spellingShingle |
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. PLoS Computational Biology |
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) |
series |
PLoS Computational Biology |
issn |
1553-734X 1553-7358 |
publishDate |
2021-07-01 |
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. |
url |
https://doi.org/10.1371/journal.pcbi.1009265 |
work_keys_str_mv |
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