Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II

Autores
Asciutto, Eliana Karina; Pantano, Sergio; General, Ignacio
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
CaMKII is a protein kinase whose function is regulated by the binding of the Calcium/Calmodulin complex (Ca2+ /CaM). It is a major player in the Long Term Potentiation process where it acts as a molecular switch, oscillating between inhibited and active conformations. The mechanism for the switching is thought to be initiated by Ca2+/CaM binding, which allows the trans-phosphorylation of a subunit of CaMKII by a neighboring kinase, leading to the active state of the system. A combination of all-atom and coarse-grained MD simulations with free energy calculations, led us to reveal an interplay of electrostatic forces exerted by Ca2+/CaM on CaMKII, which initiate the activation process. The highly electrically charged Ca2+/CaM neutralizes basic regions in the linker domain of CaMKII, facilitating its opening and consequent activation. The emerging picture of CaMKII's behavior highlights the preponderance of electrostatic interactions, which are modulated by the presence of Ca2+/CaM and the phosphorylation of key sites.
Fil: Asciutto, Eliana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; Argentina
Fil: Pantano, Sergio. Universidad Nacional de San Martín; Argentina. Instituto Pasteur de Montevideo; Uruguay
Fil: General, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; Argentina
Materia
ELECTROSTATICS
MOLECULAR DYNAMICS
COARSE-GRAINED
PHOSPHORYLATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/154520
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/154520
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase IIAsciutto, Eliana KarinaPantano, SergioGeneral, IgnacioELECTROSTATICSMOLECULAR DYNAMICSCOARSE-GRAINEDPHOSPHORYLATIONhttps://purl.org/becyt/ford/1.3https://purl.org/becyt/ford/1CaMKII is a protein kinase whose function is regulated by the binding of the Calcium/Calmodulin complex (Ca2+ /CaM). It is a major player in the Long Term Potentiation process where it acts as a molecular switch, oscillating between inhibited and active conformations. The mechanism for the switching is thought to be initiated by Ca2+/CaM binding, which allows the trans-phosphorylation of a subunit of CaMKII by a neighboring kinase, leading to the active state of the system. A combination of all-atom and coarse-grained MD simulations with free energy calculations, led us to reveal an interplay of electrostatic forces exerted by Ca2+/CaM on CaMKII, which initiate the activation process. The highly electrically charged Ca2+/CaM neutralizes basic regions in the linker domain of CaMKII, facilitating its opening and consequent activation. The emerging picture of CaMKII's behavior highlights the preponderance of electrostatic interactions, which are modulated by the presence of Ca2+/CaM and the phosphorylation of key sites.Fil: Asciutto, Eliana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; ArgentinaFil: Pantano, Sergio. Universidad Nacional de San Martín; Argentina. Instituto Pasteur de Montevideo; UruguayFil: General, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; ArgentinaElsevier Science Inc.2021-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/154520Asciutto, Eliana Karina; Pantano, Sergio; General, Ignacio; Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II; Elsevier Science Inc.; Journal Of Molecular Graphics & Modelling; 105; 107875; 6-2021; 1-141093-3263CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S1093326321000449info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jmgm.2021.107875info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:48:06Zoai:ri.conicet.gov.ar:11336/154520instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:48:06.419CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II
title Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II
spellingShingle Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II
Asciutto, Eliana Karina
ELECTROSTATICS
MOLECULAR DYNAMICS
COARSE-GRAINED
PHOSPHORYLATION
title_short Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II
title_full Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II
title_fullStr Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II
title_full_unstemmed Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II
title_sort Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II
dc.creator.none.fl_str_mv Asciutto, Eliana Karina
Pantano, Sergio
General, Ignacio
author Asciutto, Eliana Karina
author_facet Asciutto, Eliana Karina
Pantano, Sergio
General, Ignacio
author_role author
author2 Pantano, Sergio
General, Ignacio
author2_role author
author
dc.subject.none.fl_str_mv ELECTROSTATICS
MOLECULAR DYNAMICS
COARSE-GRAINED
PHOSPHORYLATION
topic ELECTROSTATICS
MOLECULAR DYNAMICS
COARSE-GRAINED
PHOSPHORYLATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv CaMKII is a protein kinase whose function is regulated by the binding of the Calcium/Calmodulin complex (Ca2+ /CaM). It is a major player in the Long Term Potentiation process where it acts as a molecular switch, oscillating between inhibited and active conformations. The mechanism for the switching is thought to be initiated by Ca2+/CaM binding, which allows the trans-phosphorylation of a subunit of CaMKII by a neighboring kinase, leading to the active state of the system. A combination of all-atom and coarse-grained MD simulations with free energy calculations, led us to reveal an interplay of electrostatic forces exerted by Ca2+/CaM on CaMKII, which initiate the activation process. The highly electrically charged Ca2+/CaM neutralizes basic regions in the linker domain of CaMKII, facilitating its opening and consequent activation. The emerging picture of CaMKII's behavior highlights the preponderance of electrostatic interactions, which are modulated by the presence of Ca2+/CaM and the phosphorylation of key sites.
Fil: Asciutto, Eliana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; Argentina
Fil: Pantano, Sergio. Universidad Nacional de San Martín; Argentina. Instituto Pasteur de Montevideo; Uruguay
Fil: General, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; Argentina
description CaMKII is a protein kinase whose function is regulated by the binding of the Calcium/Calmodulin complex (Ca2+ /CaM). It is a major player in the Long Term Potentiation process where it acts as a molecular switch, oscillating between inhibited and active conformations. The mechanism for the switching is thought to be initiated by Ca2+/CaM binding, which allows the trans-phosphorylation of a subunit of CaMKII by a neighboring kinase, leading to the active state of the system. A combination of all-atom and coarse-grained MD simulations with free energy calculations, led us to reveal an interplay of electrostatic forces exerted by Ca2+/CaM on CaMKII, which initiate the activation process. The highly electrically charged Ca2+/CaM neutralizes basic regions in the linker domain of CaMKII, facilitating its opening and consequent activation. The emerging picture of CaMKII's behavior highlights the preponderance of electrostatic interactions, which are modulated by the presence of Ca2+/CaM and the phosphorylation of key sites.
publishDate 2021
dc.date.none.fl_str_mv 2021-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/154520
Asciutto, Eliana Karina; Pantano, Sergio; General, Ignacio; Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II; Elsevier Science Inc.; Journal Of Molecular Graphics & Modelling; 105; 107875; 6-2021; 1-14
1093-3263
CONICET Digital
CONICET
url http://hdl.handle.net/11336/154520
identifier_str_mv Asciutto, Eliana Karina; Pantano, Sergio; General, Ignacio; Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II; Elsevier Science Inc.; Journal Of Molecular Graphics & Modelling; 105; 107875; 6-2021; 1-14
1093-3263
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S1093326321000449
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jmgm.2021.107875
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science Inc.
publisher.none.fl_str_mv Elsevier Science Inc.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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