Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II

Autores
Pullara, Filippo; Asciutto, Eliana Karina; General, Ignacio
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Calcium/calmodulin-dependent protein kinase II is an enzyme involved in many different functions, including the so-called long-term potentiation, a mechanism that strengthens synapses in a persistent mode and is believed to be a basic cellular mechanism for memory formation. Here we study the conformational changes of the enzyme due to phosphorylation of some key residues that are believed to drive the transition from an inhibited to an active state; it is this active state the one associated with long-term potentiation. We found that the conformational changes could be explained in terms of three charged regions in the three main subdomains of the enzyme: the hub, linker, and kinase. The role of phosphorylation is to change the charge relation between them, turning on and off their interactions and switching between an attractive state (nonphosphorylated or inhibited) and a not attractive one (phosphorylated or active). We also show that phosphorylated subunits become less stable, and this could favor their release from the multimer, as has been already observed experimentally.
Fil: Pullara, Filippo. University of Pittsburgh; Estados Unidos
Fil: Asciutto, Eliana Karina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: General, Ignacio. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Enzyme
Camkii
Molecular Dynamics
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/41361
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase IIPullara, FilippoAsciutto, Eliana KarinaGeneral, IgnacioEnzymeCamkiiMolecular Dynamicshttps://purl.org/becyt/ford/1.3https://purl.org/becyt/ford/1Calcium/calmodulin-dependent protein kinase II is an enzyme involved in many different functions, including the so-called long-term potentiation, a mechanism that strengthens synapses in a persistent mode and is believed to be a basic cellular mechanism for memory formation. Here we study the conformational changes of the enzyme due to phosphorylation of some key residues that are believed to drive the transition from an inhibited to an active state; it is this active state the one associated with long-term potentiation. We found that the conformational changes could be explained in terms of three charged regions in the three main subdomains of the enzyme: the hub, linker, and kinase. The role of phosphorylation is to change the charge relation between them, turning on and off their interactions and switching between an attractive state (nonphosphorylated or inhibited) and a not attractive one (phosphorylated or active). We also show that phosphorylated subunits become less stable, and this could favor their release from the multimer, as has been already observed experimentally.Fil: Pullara, Filippo. University of Pittsburgh; Estados UnidosFil: Asciutto, Eliana Karina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: General, Ignacio. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Chemical Society2017-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/41361Pullara, Filippo; Asciutto, Eliana Karina; General, Ignacio; Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II; American Chemical Society; Journal of Physical Chemistry B; 121; 45; 11-2017; 10344-103521520-6106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jpcb.7b09214info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:57Zoai:ri.conicet.gov.ar:11336/41361instacron: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 09:40:58.168CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II
title Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II
spellingShingle Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II
Pullara, Filippo
Enzyme
Camkii
Molecular Dynamics
title_short Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II
title_full Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II
title_fullStr Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II
title_full_unstemmed Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II
title_sort Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II
dc.creator.none.fl_str_mv Pullara, Filippo
Asciutto, Eliana Karina
General, Ignacio
author Pullara, Filippo
author_facet Pullara, Filippo
Asciutto, Eliana Karina
General, Ignacio
author_role author
author2 Asciutto, Eliana Karina
General, Ignacio
author2_role author
author
dc.subject.none.fl_str_mv Enzyme
Camkii
Molecular Dynamics
topic Enzyme
Camkii
Molecular Dynamics
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Calcium/calmodulin-dependent protein kinase II is an enzyme involved in many different functions, including the so-called long-term potentiation, a mechanism that strengthens synapses in a persistent mode and is believed to be a basic cellular mechanism for memory formation. Here we study the conformational changes of the enzyme due to phosphorylation of some key residues that are believed to drive the transition from an inhibited to an active state; it is this active state the one associated with long-term potentiation. We found that the conformational changes could be explained in terms of three charged regions in the three main subdomains of the enzyme: the hub, linker, and kinase. The role of phosphorylation is to change the charge relation between them, turning on and off their interactions and switching between an attractive state (nonphosphorylated or inhibited) and a not attractive one (phosphorylated or active). We also show that phosphorylated subunits become less stable, and this could favor their release from the multimer, as has been already observed experimentally.
Fil: Pullara, Filippo. University of Pittsburgh; Estados Unidos
Fil: Asciutto, Eliana Karina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: General, Ignacio. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Calcium/calmodulin-dependent protein kinase II is an enzyme involved in many different functions, including the so-called long-term potentiation, a mechanism that strengthens synapses in a persistent mode and is believed to be a basic cellular mechanism for memory formation. Here we study the conformational changes of the enzyme due to phosphorylation of some key residues that are believed to drive the transition from an inhibited to an active state; it is this active state the one associated with long-term potentiation. We found that the conformational changes could be explained in terms of three charged regions in the three main subdomains of the enzyme: the hub, linker, and kinase. The role of phosphorylation is to change the charge relation between them, turning on and off their interactions and switching between an attractive state (nonphosphorylated or inhibited) and a not attractive one (phosphorylated or active). We also show that phosphorylated subunits become less stable, and this could favor their release from the multimer, as has been already observed experimentally.
publishDate 2017
dc.date.none.fl_str_mv 2017-11
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/11336/41361
Pullara, Filippo; Asciutto, Eliana Karina; General, Ignacio; Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II; American Chemical Society; Journal of Physical Chemistry B; 121; 45; 11-2017; 10344-10352
1520-6106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/41361
identifier_str_mv Pullara, Filippo; Asciutto, Eliana Karina; General, Ignacio; Mechanisms of Activation and Subunit Release in Ca 2+ /Calmodulin-Dependent Protein Kinase II; American Chemical Society; Journal of Physical Chemistry B; 121; 45; 11-2017; 10344-10352
1520-6106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jpcb.7b09214
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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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