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Cell Host Microbe. 2016 Mar 9;19(3):336-48. doi: 10.1016/j.chom.2016.02.004.

HIV-1 Nucleocapsid Mimics the Membrane Adaptor Syntenin PDZ to Gain Access to ESCRTs and Promote Virus Budding.

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Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20894, USA.
Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794-8661, USA.
Electron Microscope Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Department of Global Health, University of Washington, Seattle, WA 98102, USA.
Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20894, USA. Electronic address:


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.

[Indexed for MEDLINE]
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