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dc.contributor.authorMurphy, R Elliot
dc.contributor.authorSamal, Alexandra B
dc.contributor.authorVlach, Jiri
dc.contributor.authorMas-Lloret, Vicente 
dc.contributor.authorPrevelige, Peter E
dc.contributor.authorSaad, Jamil S
dc.date.accessioned2021-05-24T10:07:13Z
dc.date.available2021-05-24T10:07:13Z
dc.date.issued2019-12
dc.identifier.citationJ Biol Chem. 2019;294(49):18600-18612.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13005
dc.description.abstractDuring the late phase of the HIV-1 replication cycle, the viral Gag polyproteins are targeted to the plasma membrane for assembly. The Gag-membrane interaction is mediated by binding of Gag's N-terminal myristoylated matrix (MA) domain to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). The viral envelope (Env) glycoprotein is then recruited to the assembly sites and incorporated into budding particles. Evidence suggests that Env incorporation is mediated by interactions between Gag's MA domain and the cytoplasmic tail of the gp41 subunit of Env (gp41CT). MA trimerization appears to be an obligatory step for this interaction. Insufficient production of a recombinant MA trimer and unavailability of a biologically relevant membrane system have been barriers to detailed structural and biophysical characterization of the putative MA-gp41CT-membrane interactions. Here, we engineered a stable recombinant HIV-1 MA trimer construct by fusing a foldon domain (FD) of phage T4 fibritin to the MA C terminus. Results from NMR experiments confirmed that the FD attachment does not adversely alter the MA structure. Employing hydrogen-deuterium exchange MS, we identified an MA-MA interface in the MA trimer that is implicated in Gag assembly and Env incorporation. Utilizing lipid nanodiscs as a membrane mimetic, we show that the MA trimer binds to membranes 30-fold tighter than does the MA monomer and that incorporation of PI(4,5)P2 and phosphatidylserine enhances the binding of MA to nanodiscs. These findings advance our understanding of a fundamental mechanism in HIV-1 assembly and provide a template for investigating the interaction of MA with gp41CT.es_ES
dc.description.sponsorshipThis work was supported by National Institutes of Health Grants 5R01GM117837 and 9R01AI150901 (to J.S.S.)es_ES
dc.language.isoenges_ES
dc.publisherAmerican Society for Biochemistry and Molecular Biologyes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectFabes_ES
dc.subjectGag proteines_ES
dc.subjectHuman immunodeficiency virus (HIV)es_ES
dc.subjectIsothermal titration calorimetry (ITC)es_ES
dc.subjectMass spectrometry (MS)es_ES
dc.subjectMyristoylated matrix (MA)es_ES
dc.subjectNanodisc (ND)es_ES
dc.subjectNuclear magnetic resonance (NMR)es_ES
dc.subjectPhosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)es_ES
dc.subjectPhosphatidylserine (PS)es_ES
dc.subjectPlasma membranees_ES
dc.subject.meshCalorimetry es_ES
dc.subject.meshCell Membrane es_ES
dc.subject.meshGene Products, gages_ES
dc.subject.meshHIV Envelope Protein gp41 es_ES
dc.subject.meshHIV-1 es_ES
dc.subject.meshMagnetic Resonance Spectroscopy es_ES
dc.subject.meshPhosphatidylserines es_ES
dc.subject.meshProtein Binding es_ES
dc.subject.meshVirus Assembly es_ES
dc.titleStructural and biophysical characterizations of HIV-1 matrix trimer binding to lipid nanodiscs shed light on virus assembly.es_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID31640987es_ES
dc.format.volume294es_ES
dc.format.number49es_ES
dc.format.page18600-18612es_ES
dc.identifier.doi10.1074/jbc.RA119.010997es_ES
dc.contributor.funderNational Institutes of Health (United States)es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1083-351Xes_ES
dc.relation.publisherversionhttps://doi.org/10.1074/jbc.RA119.010997es_ES
dc.identifier.journalThe Journal of Bological Chemistryes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Atribución 4.0 Internacional
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