Host cofactors and pharmacologic ligands share an essential interface in HIV-1 capsid that is lost upon disassembly.

ABSTRACT: The HIV-1 capsid is involved in all infectious steps from reverse transcription to integration site selection, and is the target of multiple host cell and pharmacologic ligands. However, structural studies have been limited to capsid monomers (CA), and the mechanistic basis for how these ligands influence infection is not well understood. Here we show that a multi-subunit interface formed exclusively within CA hexamers mediates binding to linear epitopes within cellular cofactors NUP153 and CPSF6, and is competed for by the antiretroviral compounds PF74 and BI-2. Each ligand is anchored via a shared phenylalanine-glycine (FG) motif to a pocket within the N-terminal domain of one monomer, and all but BI-2 also make essential interactions across the N-terminal domain: C-terminal domain (NTD:

SUBMITTER: Price AJ 

PROVIDER: S-EPMC4214760 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature