7SNQ

Hexamer HIV-1 CA in complex with CPSF6 peptide and IP6 ligand

Summary for 7SNQ

• Entry DOI: 10.2210/pdb7snq/pdb
• Descriptor: Capsid protein p24, Cleavage and polyadenylation specificity factor subunit 6, INOSITOL HEXAKISPHOSPHATE, ... (5 entities in total)
• Functional Keywords: viral protein
• Biological source: Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1); More
• Total number of polymer chains: 24
• Total formula weight: 326855.85

Authors

Bester, S.M.,Kvaratskhelia, M. (deposition date: 2021-10-28, release date: 2022-09-07, Last modification date: 2024-10-16)

Primary citation

Wei, G.,Iqbal, N.,Courouble, V.V.,Francis, A.C.,Singh, P.K.,Hudait, A.,Annamalai, A.S.,Bester, S.,Huang, S.W.,Shkriabai, N.,Briganti, L.,Haney, R.,KewalRamani, V.N.,Voth, G.A.,Engelman, A.N.,Melikyan, G.B.,Griffin, P.R.,Asturias, F.,Kvaratskhelia, M.
Prion-like low complexity regions enable avid virus-host interactions during HIV-1 infection.
Nat Commun, 13:5879-5879, 2022

PubMed Abstract: Cellular proteins CPSF6, NUP153 and SEC24C play crucial roles in HIV-1 infection. While weak interactions of short phenylalanine-glycine (FG) containing peptides with isolated capsid hexamers have been characterized, how these cellular factors functionally engage with biologically relevant mature HIV-1 capsid lattices is unknown. Here we show that prion-like low complexity regions (LCRs) enable avid CPSF6, NUP153 and SEC24C binding to capsid lattices. Structural studies revealed that multivalent CPSF6 assembly is mediated by LCR-LCR interactions, which are templated by binding of CPSF6 FG peptides to a subset of hydrophobic capsid pockets positioned along adjoining hexamers. In infected cells, avid CPSF6 LCR-mediated binding to HIV-1 cores is essential for functional virus-host interactions. The investigational drug lenacapavir accesses unoccupied hydrophobic pockets in the complex to potently impair HIV-1 inside the nucleus without displacing the tightly bound cellular cofactor from virus cores. These results establish previously undescribed mechanisms of virus-host interactions and antiviral action.

PubMed: 36202818
DOI: 10.1038/s41467-022-33662-6

Experimental method

X-RAY DIFFRACTION (2.81 Å)