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dc.contributor.authorMartínez-Bonet, Marta
dc.contributor.authorPalladino, Claudia
dc.contributor.authorBriz, Veronica 
dc.contributor.authorRudolph, Jochen M
dc.contributor.authorFackler, Oliver T
dc.contributor.authorRelloso, Miguel
dc.contributor.authorMuñoz-Fernandez, Maria Angeles
dc.contributor.authorMadrid, Ricardo
dc.identifier.citationPLoS One. 2015 Dec 23;10(12):e0145239.es_ES
dc.description.abstractTo find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121-137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection.es_ES
dc.description.sponsorshipThis work was supported by the Ramon y Cajal research program (MICIIN-RYC-2005-002174;, Fondo de Investigación Sanitaria en España (FIS-PS09/01386; to RM, and Comunidad de Madrid (S-2010/BMD-2332; to MAM-F, and the Deutsche Forschungsgemeinschaft (TRR83, project 15 to OTF). MM-B, CP and VB hold a fellowship from the Fondo de Investigación Sanitaria en España (FIS, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.publisherPublic Library of Science (PLOS) es_ES
dc.subject.meshAmino Acid Motifs es_ES
dc.subject.meshHIV-1 es_ES
dc.subject.meshHeLa Cells es_ES
dc.subject.meshHumans es_ES
dc.subject.meshProtein Structure, Tertiary es_ES
dc.subject.meshStructure-Activity Relationship es_ES
dc.subject.meshT-Lymphocytes es_ES
dc.subject.meshnef Gene Products, Human Immunodeficiency Virus es_ES
dc.titleA Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderDeutsche Forschungsgemeinschaft (Alemania) 
dc.identifier.journalPloS onees_ES
dc.rights.accessRightsopen accesses_ES

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Atribución 4.0 Internacional
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