Proteomics

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Prion-like low complexity regions enable avid virus-host interactions during HIV-1 infection


ABSTRACT: Cellular proteins CPSF6, NUP153 and SEC24C play crucial roles in HIV-1 infection. While weak interactions of short FG peptides to isolated capsid hexamers have been characterized, how these proteins engage biologically relevant extended HIV-1 capsid lattices is unknown. We have identified that prion-like low complexity regions (LCR) enable avid binding of CPSF6, NUP153 and SEC24C to curved hexameric capsid lattices. Structural studies reveal that LCR-LCR interactions mediate multivalent CPSF6 assembly, which are templated by binding of CPSF6 FG peptides to a subset of hydrophobic capsid pockets positioned along adjoining hexamers. CPSF6 LCR mediated avid binding to HIV-1 cores is essential for functional virus-host interactions in infected cells. Investigational drug lenacapavir can access unoccupied hydrophobic pockets in the CPSF6-HIV-1 complex and potently impair HIV-1 inside the nucleus without displacing the tightly bound cellular cofactor from virus cores. These results elucidate previously undescribed mechanisms of virus-host interactions and potent inhibition of HIV-1.

INSTRUMENT(S): Q Exactive HF, Q Exactive

ORGANISM(S): Homo Sapiens (human) Human Immunodeficiency Virus

SUBMITTER: Valentine Courouble  

LAB HEAD: Patrick Griffin

PROVIDER: PXD030332 | Pride | 2022-08-31

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
CaA92E_MSMS_Pepsin_01M_NaPhos_TCEP.mgf Mgf
CaA92E_MSMS_Pepsin_01M_NaPhos_TCEP.raw Raw
CaAE_CaAEGSTCPSF6_10_1.raw Raw
CaAE_CaAEGSTCPSF6_10_2.raw Raw
CaAE_CaAEGSTCPSF6_10_3.raw Raw
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