Two-step ATP-driven opening of cohesin head

Abstract The cohesin ring is a protein complex composed of four core subunits: Smc1A, Smc3, Rad21 and Stag1/2. It is involved in chromosome segregation, DNA repair, chromatin organization and transcription regulation. Opening of the ring occurs at the “head” structure, formed of the ATPase domains o...

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Autores principales:	Íñigo Marcos-Alcalde, Jesús I. Mendieta-Moreno, Beatriz Puisac, María Concepción Gil-Rodríguez, María Hernández-Marcos, Diego Soler-Polo, Feliciano J. Ramos, José Ortega, Juan Pié, Jesús Mendieta, Paulino Gómez-Puertas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9d8b866162dc4999b46b4c8eaf6a54fb
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spelling	oai:doaj.org-article:9d8b866162dc4999b46b4c8eaf6a54fb2021-12-02T15:06:18ZTwo-step ATP-driven opening of cohesin head10.1038/s41598-017-03118-92045-2322https://doaj.org/article/9d8b866162dc4999b46b4c8eaf6a54fb2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03118-9https://doaj.org/toc/2045-2322Abstract The cohesin ring is a protein complex composed of four core subunits: Smc1A, Smc3, Rad21 and Stag1/2. It is involved in chromosome segregation, DNA repair, chromatin organization and transcription regulation. Opening of the ring occurs at the “head” structure, formed of the ATPase domains of Smc1A and Smc3 and Rad21. We investigate the mechanisms of the cohesin ring opening using techniques of free molecular dynamics (MD), steered MD and quantum mechanics/molecular mechanics MD (QM/MM MD). The study allows the thorough analysis of the opening events at the atomic scale: i) ATP hydrolysis at the Smc1A site, evaluating the role of the carboxy-terminal domain of Rad21 in the process; ii) the activation of the Smc3 site potentially mediated by the movement of specific amino acids; and iii) opening of the head domains after the two ATP hydrolysis events. Our study suggests that the cohesin ring opening is triggered by a sequential activation of the ATP sites in which ATP hydrolysis at the Smc1A site induces ATPase activity at the Smc3 site. Our analysis also provides an explanation for the effect of pathogenic variants related to cohesinopathies and cancer.Íñigo Marcos-AlcaldeJesús I. Mendieta-MorenoBeatriz PuisacMaría Concepción Gil-RodríguezMaría Hernández-MarcosDiego Soler-PoloFeliciano J. RamosJosé OrtegaJuan PiéJesús MendietaPaulino Gómez-PuertasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Íñigo Marcos-Alcalde Jesús I. Mendieta-Moreno Beatriz Puisac María Concepción Gil-Rodríguez María Hernández-Marcos Diego Soler-Polo Feliciano J. Ramos José Ortega Juan Pié Jesús Mendieta Paulino Gómez-Puertas Two-step ATP-driven opening of cohesin head
description	Abstract The cohesin ring is a protein complex composed of four core subunits: Smc1A, Smc3, Rad21 and Stag1/2. It is involved in chromosome segregation, DNA repair, chromatin organization and transcription regulation. Opening of the ring occurs at the “head” structure, formed of the ATPase domains of Smc1A and Smc3 and Rad21. We investigate the mechanisms of the cohesin ring opening using techniques of free molecular dynamics (MD), steered MD and quantum mechanics/molecular mechanics MD (QM/MM MD). The study allows the thorough analysis of the opening events at the atomic scale: i) ATP hydrolysis at the Smc1A site, evaluating the role of the carboxy-terminal domain of Rad21 in the process; ii) the activation of the Smc3 site potentially mediated by the movement of specific amino acids; and iii) opening of the head domains after the two ATP hydrolysis events. Our study suggests that the cohesin ring opening is triggered by a sequential activation of the ATP sites in which ATP hydrolysis at the Smc1A site induces ATPase activity at the Smc3 site. Our analysis also provides an explanation for the effect of pathogenic variants related to cohesinopathies and cancer.
format	article
author	Íñigo Marcos-Alcalde Jesús I. Mendieta-Moreno Beatriz Puisac María Concepción Gil-Rodríguez María Hernández-Marcos Diego Soler-Polo Feliciano J. Ramos José Ortega Juan Pié Jesús Mendieta Paulino Gómez-Puertas
author_facet	Íñigo Marcos-Alcalde Jesús I. Mendieta-Moreno Beatriz Puisac María Concepción Gil-Rodríguez María Hernández-Marcos Diego Soler-Polo Feliciano J. Ramos José Ortega Juan Pié Jesús Mendieta Paulino Gómez-Puertas
author_sort	Íñigo Marcos-Alcalde
title	Two-step ATP-driven opening of cohesin head
title_short	Two-step ATP-driven opening of cohesin head
title_full	Two-step ATP-driven opening of cohesin head
title_fullStr	Two-step ATP-driven opening of cohesin head
title_full_unstemmed	Two-step ATP-driven opening of cohesin head
title_sort	two-step atp-driven opening of cohesin head
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9d8b866162dc4999b46b4c8eaf6a54fb
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Two-step ATP-driven opening of cohesin head

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