Estudios de RMN del dominio sensor de calcio del intercambiador de Na+ /Ca2+ de Drosophila melanogaster

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dc.contributor.advisorKopke Salinas, Roberto
dc.contributor.advisorEspejo Benavides, Blanca Fabiola
dc.contributor.authorRodríguez Pineda, Mario Andrés
dc.contributor.researchgroupMetabolismo de Calcio y Mecanismos de competición entre microorganismosspa
dc.date.accessioned2022-01-31T18:29:58Z
dc.date.available2022-01-31T18:29:58Z
dc.date.issued2020
dc.descriptionilustraciones, diagramas, tablasspa
dc.description.abstractLos intercambiadores de sodio-calcio (Na+ /Ca2+ exchangers, NCX) componen una amplia familia de intercambiadores presentes en casi todos los organismos, estando involucrados en la homeostasis celular del Ca2+. Una de estas proteínas de intercambio iónico que ha presentado gran interés para los científicos es el intercambiador (CALX) de Drosophila melanogaster (mosca de la fruta), debido a que la presencia de Ca2+ intracelular inhibe el intercambio iónico en CALX, mientras que en mamíferos (especialmente en NCX1) el incremento de [Ca2+]i activa el intercambiador. A demás de la diferencia con NCX, CALX presenta dos isoformas gracias al empalme (splicing) alternativo llamadas CALX-1.1 y CALX-1.2. Estas isoformas se diferencian por la mutación de 5 aminoácidos en el loop-FG de CBD2 y, porque CALX-1.1 es altamente inhibida por la presencia de Ca2+ mientras que la inhibición en CALX-1.2 es mucho menor, al punto que algunos autores llegan a establecer que es insensible al Ca2+i. Para comprender estas diferencias entre las dos isoformas de CALX, en este trabajo se llevaron a cabo estudios de dinámica molecular tanto del dominio CBD2 como del conjunto de CBD1 y CBD2 (denominado CBD12), encontrando diferencias dinámicas en CBD2, principalmente en la región del loop-FG. Según lo observado la hélice 1 en el loop-FG en CBD2 puede interactuar con la R584 en el loop-CD del mismo dominio en la isoforma 1.2 de mejor manera que en la isoforma 1.1, especialmente en la forma coordinada a Ca2+, lo que permite que CBD12 posea una orientación más compacta lo que hace que la isoforma 1.2 sea menos sensible al Ca2+ que la isoforma 1.1 (Texto tomado de la fuente)spa
dc.description.abstractSodium-calcium exchangers (Na+ /Ca2+ exchangers, NCX) are a wide family of exchangers present in almost all organisms, being involved in Ca2+ cellular homeostasis. One of these ion exchange proteins that has been of great interest to scientists is the Drosophila melanogaster (fruit fly) exchanger (CALX), because the presence of intracellular Ca2+ inhibits ion exchange in CALX, whereas in mammals (especially in NCX1) the increase of [Ca2+]i activates the exchanger. In addition to the difference with NCX, CALX presents two isoforms thanks to the alternative splicing called CALX-1.1 and CALX-1.2. These isoforms are differentiated by the 5 amino acid mutation in the CBD2 loop-FG and, because CALX-1.1 is highly inhibited by the presence of Ca2+ while the inhibition in CALX-1.2 is much lower, to the point that some authors reach establish that it is insensitive to Ca2+i. To understand these differences between the two CALX isoforms, in this work molecular dynamics studies of both the CBD2 domain and the set of CBD1 and CBD2 (called CBD12) were carried out, finding dynamic differences in CBD2, mainly in the FG-loop region. As observed helix 1 in FG-loop in CBD2 can interact with R584 in CD-loop of the same domain in 1.2 isoform better than in 1.1 isoform, especially in the Ca2+ binding form, allowing CBD12 has a more compact orientation making the 1.2 isoform less sensitive to Ca2+i than the 1.1 isoformeng
dc.description.curricularareaÁrea Curricular de Bioctecnologíaspa
dc.description.degreelevelDoctoradospa
dc.description.degreenameDoctor en Biotecnologíaspa
dc.description.funderConvocatoria No. 647 de 2014spa
dc.description.researchareaBiología estructural y bioquímicaspa
dc.description.sponsorshipCOLCIENCIASspa
dc.format.extentxx, 123 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps:/repositorio.una.edu.cospa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/80816
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Medellínspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeMedellín, Colombiaspa
dc.publisher.programMedellín - Ciencias - Doctorado en Biotecnologíaspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial-SinDerivadas 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/spa
dc.subject.ddc660 - Ingeniería químicaspa
dc.subject.lembDinámica molecular
dc.subject.lembMolecular dynamics
dc.subject.proposalIntercambiadores Na+ /Ca2+spa
dc.subject.proposalDinámica de Proteínasspa
dc.subject.proposalEspectroscopia de Resonancia Magnética Nuclearspa
dc.subject.proposalSimulaciones de Dinámica Molecularspa
dc.subject.proposalNa+ /Ca2+ Exchangerseng
dc.subject.proposalMolecular Dynamics Simulationseng
dc.subject.proposalNuclear Magnetic Resonance Spectroscopyeng
dc.subject.proposalProtein Dynamicseng
dc.titleEstudios de RMN del dominio sensor de calcio del intercambiador de Na+ /Ca2+ de Drosophila melanogasterspa
dc.title.translatedNMR studies of the calcium sensing domain of the Na+ /Ca2+ exchanger of Drosophila melanogastereng
dc.typeTrabajo de grado - Doctoradospa
dc.type.coarhttp://purl.org/coar/resource_type/c_db06spa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
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dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
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oaire.fundernameFAPESPspa

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