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TitleStructural insights into HIV-2 CA lattice formation and FG-pocket binding revealed by single-particle cryo-EM.
Journal, issue, pagesCell Rep, Vol. 44, Issue 2, Page 115245, Year 2025
Publish dateFeb 25, 2025
AuthorsMatthew Cook / Christian Freniere / Chunxiang Wu / Faith Lozano / Yong Xiong /
PubMed AbstractOne of the striking features of human immunodeficiency virus (HIV) is the capsid, a fullerene cone comprised of pleomorphic capsid protein (CA) that shields the viral genome and recruits cofactors. ...One of the striking features of human immunodeficiency virus (HIV) is the capsid, a fullerene cone comprised of pleomorphic capsid protein (CA) that shields the viral genome and recruits cofactors. Despite significant advances in understanding the mechanisms of HIV-1 CA assembly and host factor interactions, HIV-2 CA assembly remains poorly understood. By templating the assembly of HIV-2 CA on functionalized liposomes, we report high-resolution structures of the HIV-2 CA lattice, including both CA hexamers and pentamers, alone and with peptides of host phenylalanine-glycine (FG)-motif proteins Nup153 and CPSF6. While the overall fold and mode of FG-peptide binding is conserved with HIV-1, this study reveals distinctive features of the HIV-2 CA lattice, including differing structural character at regions of host factor interactions and divergence in the mechanism of formation of CA hexamers and pentamers. This study extends our understanding of HIV capsids and highlights an approach facilitating the study of lentiviral capsid biology.
External linksCell Rep / PubMed:39864060 / PubMed Central
MethodsEM (single particle)
Resolution1.98 - 3.25 Å
Structure data

EMDB-45676, PDB-9clj:
HIV-2 CA T=1 Icosahedron; assembled via lipid templating
Method: EM (single particle) / Resolution: 1.98 Å

EMDB-45758, PDB-9cns:
HIV-2 CA hexamer; assembled via liposome templating
Method: EM (single particle) / Resolution: 3.25 Å

EMDB-45759, PDB-9cnt:
HIV-2 CA pentamer; assembled via liposome templating
Method: EM (single particle) / Resolution: 2.97 Å

EMDB-45760, PDB-9cnu:
HIV-2 CA hexamer bound with Nup153 peptide; assembled with liposome templating
Method: EM (single particle) / Resolution: 2.99 Å

EMDB-45761, PDB-9cnv:
HIV-2 CA hexamer bound with CPSF6 peptide; assembled via liposome templating
Method: EM (single particle) / Resolution: 3.16 Å

EMDB-45762: HIV-2 CA pentamer in the presence of Nup153 peptide but without binding; assembled via liposome templating
Method: EM (single particle) / Resolution: 2.98 Å

EMDB-45763: HIV-2 CA pentamer in the presence of CPSF6 peptide but without binding; assembled via liposome templating
Method: EM (single particle) / Resolution: 2.82 Å

EMDB-47600: HIV-1 Global CA Pentamer Assembled by Liposome Templating on Small Unilamellar Vesicles
Method: EM (single particle) / Resolution: 3.07 Å

Chemicals

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE

ChemComp-HOH:
WATER

Source
  • human immunodeficiency virus 2
  • homo sapiens (human)
  • Human immunodeficiency virus 1
KeywordsVIRAL PROTEIN / HIV-2 / Capsid / IP6 / Nup153 / CPSF6

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