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dc.contributor.authorGarrido, Francisco
dc.contributor.authorPacheco, María
dc.contributor.authorVargas-Martínez, Rocío
dc.contributor.authorVelasco-García, Roberto
dc.contributor.authorJorge, Inmaculada 
dc.contributor.authorSerrano, Horacio
dc.contributor.authorPortillo, Francisco
dc.contributor.authorVazquez, Jesus 
dc.contributor.authorPajares, María Ángeles
dc.date.accessioned2019-02-07T11:14:13Z
dc.date.available2019-02-07T11:14:13Z
dc.date.issued2018
dc.identifier.citationPLoS One. 2018; 13(6):e0199472es_ES
dc.identifier.issn1932-6203es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7136
dc.description.abstractProtein-protein interactions are an important mechanism for the regulation of enzyme function allowing metabolite channeling, crosstalk between pathways or the introduction of post-translational modifications. Therefore, a number of high-throughput studies have been carried out to shed light on the protein networks established under different pathophysiological settings. Surprisingly, this type of information is quite limited for enzymes of intermediary metabolism such as betaine homocysteine S-methyltransferase, despite its high hepatic abundancy and its role in homocysteine metabolism. Here, we have taken advantage of two approaches, affinity purification combined with mass spectrometry and yeast two-hybrid, to further uncover the array of interactions of betaine homocysteine S-methyltransferase in normal liver of Rattus norvegicus. A total of 131 non-redundant putative interaction targets were identified, out of which 20 were selected for further validation by coimmunoprecipitation. Interaction targets validated by two different methods include: S-methylmethionine homocysteine methyltransferase or betaine homocysteine methyltransferase 2, methionine adenosyltransferases α1 and α2, cAMP-dependent protein kinase catalytic subunit alpha, 4-hydroxyphenylpyruvic acid dioxygenase and aldolase b. Network analysis identified 122 nodes and 165 edges, as well as a limited number of KEGG pathways that comprise: the biosynthesis of amino acids, cysteine and methionine metabolism, the spliceosome and metabolic pathways. These results further expand the connections within the hepatic methionine cycle and suggest putative cross-talks with additional metabolic pathways that deserve additional research.es_ES
dc.description.sponsorshipThis work was supported by grants of the Ministerio de Economıa, Industria y Competitividad (BFU2005-00050, BFU2008-00666, BFU200908977 to MAP; BFU2008-04285 to FP). The CNIC is supported by the Ministerio de Economıa, Industria y Competitividad (MEIC) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleIdentification of hepatic protein-protein interaction targets for betaine homocysteine S-methyltransferasees_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29924862es_ES
dc.format.volume13es_ES
dc.format.number6es_ES
dc.format.pagee0199472es_ES
dc.identifier.doi10.1371/journal.pone.0199472es_ES
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España)
dc.contributor.funderFundación ProCNIC
dc.description.peerreviewedes_ES
dc.identifier.e-issn1932-6203es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0199472es_ES
dc.identifier.journalPloS onees_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Proteómica cardiovasculares_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2005-00050es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2008-00666es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2009-08977es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2008-04285es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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