Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity

Autores
Albano, Juan Manuel Ricardo; Mussini, Nahuel; Toriano, Roxana Mabel; Facelli, Julio C.; Ferraro, Marta Beatriz; Pickholz, Mónica Andrea
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Connexinophaties are a collective of diseases related to connexin channels and hemichannels. In particular many Cx26 alterations are strongly associated to human deafness. Calcium plays an important role on this structures regulation. Here, using calcium as a probe, extensive atomistic Molecular Dynamics simulations were performed on the Cx26 hemichannel embedded in a lipid bilayer. Exploring different initial conditions and calcium concentration, simulation reached ∼4 μs. Several analysis were carried out in order to reveal the calcium distribution and localization, such as electron density profiles, density maps and distance time evolution, which is directly associated to the interaction energy. Specific amino acid interactions with calcium and their stability were capture within this context. Few of these sites such as, GLU42, GLU47, GLY45 and ASP50, were already suggested in the literature. Besides, we identified novel calcium biding sites: ASP2, ASP117, ASP159, GLU114, GLU119, GLU120 and VAL226. To the best of our knowledge, this is the first time that these sites are reported within this context. Furthermore, since various pathologies involving the Cx26 hemichannel are associated with pathogenic variants in the corresponding CJB2 gene, using ClinVar, we were able to spatially associate the 3D positions of the identified calcium binding sites within the framework of this work with reported pathogenic variants in the CJB2 gene. This study presents a first step on finding associations between molecular features and pathological variants of the Cx26 hemichannel.
Fil: Albano, Juan Manuel Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
Fil: Mussini, Nahuel. Universidad de Buenos Aires; Argentina
Fil: Toriano, Roxana Mabel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Biomembranas; Argentina
Fil: Facelli, Julio C.. University of Utah; Estados Unidos
Fil: Ferraro, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina
Fil: Pickholz, Mónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
Materia
CONNEXIN
MOLECULAR DYNAMICS
POPC
VARIANT ANNOTATION
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:11336/86139
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicityAlbano, Juan Manuel RicardoMussini, NahuelToriano, Roxana MabelFacelli, Julio C.Ferraro, Marta BeatrizPickholz, Mónica AndreaCONNEXINMOLECULAR DYNAMICSPOPCVARIANT ANNOTATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Connexinophaties are a collective of diseases related to connexin channels and hemichannels. In particular many Cx26 alterations are strongly associated to human deafness. Calcium plays an important role on this structures regulation. Here, using calcium as a probe, extensive atomistic Molecular Dynamics simulations were performed on the Cx26 hemichannel embedded in a lipid bilayer. Exploring different initial conditions and calcium concentration, simulation reached ∼4 μs. Several analysis were carried out in order to reveal the calcium distribution and localization, such as electron density profiles, density maps and distance time evolution, which is directly associated to the interaction energy. Specific amino acid interactions with calcium and their stability were capture within this context. Few of these sites such as, GLU42, GLU47, GLY45 and ASP50, were already suggested in the literature. Besides, we identified novel calcium biding sites: ASP2, ASP117, ASP159, GLU114, GLU119, GLU120 and VAL226. To the best of our knowledge, this is the first time that these sites are reported within this context. Furthermore, since various pathologies involving the Cx26 hemichannel are associated with pathogenic variants in the corresponding CJB2 gene, using ClinVar, we were able to spatially associate the 3D positions of the identified calcium binding sites within the framework of this work with reported pathogenic variants in the CJB2 gene. This study presents a first step on finding associations between molecular features and pathological variants of the Cx26 hemichannel.Fil: Albano, Juan Manuel Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Mussini, Nahuel. Universidad de Buenos Aires; ArgentinaFil: Toriano, Roxana Mabel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Biomembranas; ArgentinaFil: Facelli, Julio C.. University of Utah; Estados UnidosFil: Ferraro, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Pickholz, Mónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaElsevier2018-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/86139Albano, Juan Manuel Ricardo; Mussini, Nahuel; Toriano, Roxana Mabel; Facelli, Julio C.; Ferraro, Marta Beatriz; et al.; Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity; Elsevier; Computational Biology And Chemistry; 77; 12-2018; 331-3421476-9271CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.compbiolchem.2018.11.004info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:08:40Zoai:ri.conicet.gov.ar:11336/86139instacron: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:34982025-11-05 10:08:40.98CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity
title Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity
spellingShingle Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity
Albano, Juan Manuel Ricardo
CONNEXIN
MOLECULAR DYNAMICS
POPC
VARIANT ANNOTATION
title_short Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity
title_full Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity
title_fullStr Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity
title_full_unstemmed Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity
title_sort Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity
dc.creator.none.fl_str_mv Albano, Juan Manuel Ricardo
Mussini, Nahuel
Toriano, Roxana Mabel
Facelli, Julio C.
Ferraro, Marta Beatriz
Pickholz, Mónica Andrea
author Albano, Juan Manuel Ricardo
author_facet Albano, Juan Manuel Ricardo
Mussini, Nahuel
Toriano, Roxana Mabel
Facelli, Julio C.
Ferraro, Marta Beatriz
Pickholz, Mónica Andrea
author_role author
author2 Mussini, Nahuel
Toriano, Roxana Mabel
Facelli, Julio C.
Ferraro, Marta Beatriz
Pickholz, Mónica Andrea
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CONNEXIN
MOLECULAR DYNAMICS
POPC
VARIANT ANNOTATION
topic CONNEXIN
MOLECULAR DYNAMICS
POPC
VARIANT ANNOTATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Connexinophaties are a collective of diseases related to connexin channels and hemichannels. In particular many Cx26 alterations are strongly associated to human deafness. Calcium plays an important role on this structures regulation. Here, using calcium as a probe, extensive atomistic Molecular Dynamics simulations were performed on the Cx26 hemichannel embedded in a lipid bilayer. Exploring different initial conditions and calcium concentration, simulation reached ∼4 μs. Several analysis were carried out in order to reveal the calcium distribution and localization, such as electron density profiles, density maps and distance time evolution, which is directly associated to the interaction energy. Specific amino acid interactions with calcium and their stability were capture within this context. Few of these sites such as, GLU42, GLU47, GLY45 and ASP50, were already suggested in the literature. Besides, we identified novel calcium biding sites: ASP2, ASP117, ASP159, GLU114, GLU119, GLU120 and VAL226. To the best of our knowledge, this is the first time that these sites are reported within this context. Furthermore, since various pathologies involving the Cx26 hemichannel are associated with pathogenic variants in the corresponding CJB2 gene, using ClinVar, we were able to spatially associate the 3D positions of the identified calcium binding sites within the framework of this work with reported pathogenic variants in the CJB2 gene. This study presents a first step on finding associations between molecular features and pathological variants of the Cx26 hemichannel.
Fil: Albano, Juan Manuel Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
Fil: Mussini, Nahuel. Universidad de Buenos Aires; Argentina
Fil: Toriano, Roxana Mabel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Biomembranas; Argentina
Fil: Facelli, Julio C.. University of Utah; Estados Unidos
Fil: Ferraro, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina
Fil: Pickholz, Mónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
description Connexinophaties are a collective of diseases related to connexin channels and hemichannels. In particular many Cx26 alterations are strongly associated to human deafness. Calcium plays an important role on this structures regulation. Here, using calcium as a probe, extensive atomistic Molecular Dynamics simulations were performed on the Cx26 hemichannel embedded in a lipid bilayer. Exploring different initial conditions and calcium concentration, simulation reached ∼4 μs. Several analysis were carried out in order to reveal the calcium distribution and localization, such as electron density profiles, density maps and distance time evolution, which is directly associated to the interaction energy. Specific amino acid interactions with calcium and their stability were capture within this context. Few of these sites such as, GLU42, GLU47, GLY45 and ASP50, were already suggested in the literature. Besides, we identified novel calcium biding sites: ASP2, ASP117, ASP159, GLU114, GLU119, GLU120 and VAL226. To the best of our knowledge, this is the first time that these sites are reported within this context. Furthermore, since various pathologies involving the Cx26 hemichannel are associated with pathogenic variants in the corresponding CJB2 gene, using ClinVar, we were able to spatially associate the 3D positions of the identified calcium binding sites within the framework of this work with reported pathogenic variants in the CJB2 gene. This study presents a first step on finding associations between molecular features and pathological variants of the Cx26 hemichannel.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
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/11336/86139
Albano, Juan Manuel Ricardo; Mussini, Nahuel; Toriano, Roxana Mabel; Facelli, Julio C.; Ferraro, Marta Beatriz; et al.; Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity; Elsevier; Computational Biology And Chemistry; 77; 12-2018; 331-342
1476-9271
CONICET Digital
CONICET
url http://hdl.handle.net/11336/86139
identifier_str_mv Albano, Juan Manuel Ricardo; Mussini, Nahuel; Toriano, Roxana Mabel; Facelli, Julio C.; Ferraro, Marta Beatriz; et al.; Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity; Elsevier; Computational Biology And Chemistry; 77; 12-2018; 331-342
1476-9271
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.compbiolchem.2018.11.004
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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