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-Structure paper
Title | A molecular switch modulates assembly and host factor binding of the HIV-1 capsid. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 30, Issue 3, Page 383-390, Year 2023 |
Publish date | Feb 9, 2023 |
Authors | Randall T Schirra / Nayara F B Dos Santos / Kaneil K Zadrozny / Iga Kucharska / Barbie K Ganser-Pornillos / Owen Pornillos / |
PubMed Abstract | The 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 ...The 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 3 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. |
External links | Nat Struct Mol Biol / PubMed:36759579 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.2 - 3.9 Å |
Structure data | EMDB-26715, PDB-7urn: EMDB-26718, PDB-7urt: EMDB-28054, PDB-8eep: EMDB-28057, PDB-8eet: EMDB-28186, PDB-8ejl: |
Chemicals | ChemComp-IHP: |
Source |
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Keywords | VIRUS LIKE PARTICLE / HIV-1 / capsid / declination / pentamer / hexamer / VIRAL PROTEIN |