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HIV-1 Nef Uses a Conserved Pocket to Recruit the N-Terminal Cytoplasmic Tail of Serinc3.


ABSTRACT: Human transmembrane proteins Serinc3 and Serinc5 are antiviral restriction factors that inhibit HIV-1 infectivity. In the absence of viral antagonism, Serinc3 and Serinc5 incorporate into the envelopes of nascent virions and inhibit the fusion of virions to the target cells. The HIV-1 virus counteracts the restriction of Serinc3 by downregulating it from the cell surface and thus excluding it from budding virions. This is orchestrated by the viral accessory protein Nef and involves hijacking of the clathrin adaptor protein complex 2 (AP2)-dependent endocytosis. The mechanistic details of Nef-mediated Serinc3 downregulation, however, have been enigmatic. In this work, we investigated and revealed the molecular determinants of Serinc3 modulation by Nef. Our results show that Nef recruits Ser

SUBMITTER: Karimian Shamsabadi M 

PROVIDER: S-EPMC12846431 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature