title: HIV-1 Nucleocapsid Mimics the Membrane Adaptor Syntenin PDZ to Gain Access to ESCRTs and Promote Virus Budding.
abstract: HIV-1 recruits cellular endosomal sorting complexes required for transport (ESCRTs) to bud virions from the membrane. Disruption of the viral nucleocapsid (NC) domain integrity affects HIV-1 budding. However, the molecular mechanisms of NC's involvement in HIV budding remain unclear. We find that NC mimics the PDZ domains of syntenin, a membrane-binding adaptor involved in cell-to-cell contact/communication, to capture the Bro1 domain of ALIX, which is an ESCRTs recruiting cellular adaptor. NC binds membranes via basic residues in either the distal or proximal zinc fingers, and NC-membrane binding is essential for Bro1 capture and HIV-1 budding. Removal of RNA enhances NC membrane binding, suggesting a dynamic competition between membrane lipids and RNA for the same binding sites in NC. Remarkably, syntenin PDZ can substitute for NC function in HIV-1 budding. Thus, NC mimics syntenin PDZs to function as a membrane-binding adaptor critical for HIV-1 budding at specific microdomains of the membrane.
authors.affiliation: Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20894, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Sette
authors.affiliation: Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20894, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: O'Connor
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794-8661, USA.
authors.forename: V Siddartha
authors.initials: VS
authors.lastname: Yerramilli
authors.affiliation: Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20894, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Dussupt
authors.affiliation: Electron Microscope Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
authors.forename: Kunio
authors.initials: K
authors.lastname: Nagashima
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA 98102, USA.
authors.forename: Kasana
authors.initials: K
authors.lastname: Chutiraka
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA 98102, USA.
authors.forename: Jaisri
authors.initials: J
authors.lastname: Lingappa
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794-8661, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Scarlata
authors.affiliation: Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20894, USA. Electronic address: bouamrf@mail.nih.gov.
authors.forename: Fadila
authors.initials: F
authors.lastname: Bouamr
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D013601:T-Lymphocytes / Q000821:virology*; D057074:Virus Release; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C080114:NC71 protein, Human immunodeficiency virus 1; C117020:PDCD6IP protein, human; D054301:gag Gene Products, Human Immunodeficiency Virus