Structural highlights
Publication Abstract from PubMed
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(10) 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.
A molecular switch modulates assembly and host factor binding of the HIV-1 capsid.,Schirra RT, Dos Santos NFB, Zadrozny KK, Kucharska I, Ganser-Pornillos BK, Pornillos O Nat Struct Mol Biol. 2023 Mar;30(3):383-390. doi: 10.1038/s41594-022-00913-5. , Epub 2023 Feb 9. PMID:36759579[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schirra RT, Dos Santos NFB, Zadrozny KK, Kucharska I, Ganser-Pornillos BK, Pornillos O. A molecular switch modulates assembly and host factor binding of the HIV-1 capsid. Nat Struct Mol Biol. 2023 Mar;30(3):383-390. PMID:36759579 doi:10.1038/s41594-022-00913-5
