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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.

Author information

1
Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20894, USA.
2
Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794-8661, USA.
3
Electron Microscope Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
4
Department of Global Health, University of Washington, Seattle, WA 98102, USA.
5
Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20894, USA. Electronic address: bouamrf@mail.nih.gov.

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.

PMID:
26962944
PMCID:
PMC4804359
DOI:
10.1016/j.chom.2016.02.004
[Indexed for MEDLINE]
Free PMC Article

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