8EJL

Structure of HIV-1 capsid declination in complex with CPSF6-FG peptide

Summary for 8EJL

• Entry DOI: 10.2210/pdb8ejl/pdb
• Related: 7URN
• EMDB information: 28186
• Descriptor: HIV-1 capsid protein, Cleavage and polyadenylation specificity factor subunit 6 (2 entities in total)
• Functional Keywords: hiv-1, capsid, declination, pentamer, hexamer, viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 105939.61

Authors

Pornillos, O.,Ganser-Pornillos, B.K.,Schirra, R.T.,dos Santos, N.F.B. (deposition date: 2022-09-17, release date: 2023-02-15, Last modification date: 2024-06-19)

Primary citation

Schirra, R.T.,Dos Santos, N.F.B.,Zadrozny, K.K.,Kucharska, I.,Ganser-Pornillos, B.K.,Pornillos, O.
A molecular switch modulates assembly and host factor binding of the HIV-1 capsid.
Nat.Struct.Mol.Biol., 30:383-390, 2023

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 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.

PubMed: 36759579
DOI: 10.1038/s41594-022-00913-5

Experimental method

ELECTRON MICROSCOPY (3.9 Å)