• Medientyp: E-Artikel
  • Titel: A molecular switch modulates assembly and host factor binding of the HIV-1 capsid
  • Beteiligte: Schirra, Randall T.; dos Santos, Nayara F. B.; Zadrozny, Kaneil K.; Kucharska, Iga; Ganser-Pornillos, Barbie K.; Pornillos, Owen
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: Nature Structural & Molecular Biology (2023)
  • Sprache: Englisch
  • DOI: 10.1038/s41594-022-00913-5
  • ISSN: 1545-9993; 1545-9985
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  • Beschreibung: AbstractThe HIV-1 capsid is a fullerene cone made of quasi-equivalent hexamers and pentamers of the viral CA protein. Typically, quasi-equivalent assembly of viral capsid subunits is controlled by a molecular switch. Here, we identify a Thr-Val-Gly-Gly motif that modulates CA hexamer/pentamer switching by folding into a 310 helix in the pentamer and random coil in the hexamer. Manipulating the coil/helix configuration of the motif allowed us to control pentamer and hexamer formation in a predictable manner, thus proving its function as a molecular switch. Importantly, the switch also remodels the common binding site for host factors that are critical for viral replication and the new ultra-potent HIV-1 inhibitor lenacapavir. This study reveals that a critical assembly element also modulates the post-assembly and viral replication functions of the HIV-1 capsid and provides new insights on capsid function and inhibition.