ArticleJournal of virology2008
A diacidic motif in human immunodeficiency virus type 1 Nef is a novel determinant of binding to AP-2.
Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- Article
- An Amino Acid Polymorphism within the HIV-1 Nef Dileucine Motif Functionally Uncouples Cell Surface CD4 and SERINC5 Downregulation.Journal of virology · 2021Article
- Mechanism of p38 MAPK-induced EGFR endocytosis and its crosstalk with ligand-induced pathways.The Journal of cell biology · 2021Article
- HIV-1 Nef-Induced Secretion of the Proinflammatory Protease TACE into Extracellular Vesicles Is Mediated by Raf-1 and Can Be Suppressed by Clinical Protein Kinase Inhibitors.Journal of virology · 2021Article
- Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction.Viruses · 2021Article
- Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals.Scientific reports · 2020Article
- Hijacking of endocytosis by HIV-1 Nef is becoming crystal clear.Nature structural & molecular biology · 2020Article
- The Nef Protein of the Macrophage Tropic HIV-1 Strain AD8 Counteracts Human BST-2/Tetherin.Viruses · 2020Article
- Two Functional Variants of AP-1 Complexes Composed of either γ2 or γ1 Subunits Are Independently Required for Major Histocompatibility Complex Class I Downregulation by HIV-1 Nef.Journal of virology · 2020Article
- Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant.PloS one · 2020Article
- How HIV Nef Proteins Hijack Membrane Traffic To Promote Infection.Journal of virology · 2019Review
- Article
- Article
- HSPA12A targets the cytoplasmic domain and affects the trafficking of the Amyloid Precursor Protein receptor SorLA.Scientific reports · 2019Article
- HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection.Frontiers in microbiology · 2019Article
- Maintenance of AP-2-Dependent Functional Activities of Nef Restricts Pathways of Immune Escape from CD8 T Lymphocyte Responses.Journal of virology · 2018Article
- The tripartite leader sequence is required for ectopic expression of HAdV-B and HAdV-E E3 CR1 genes.Virology · 2017Article
- Cell-based Fluorescence Complementation Reveals a Role for HIV-1 Nef Protein Dimerization in AP-2 Adaptor Recruitment and CD4 Co-receptor Down-regulation.The Journal of biological chemistry · 2017Article
- The Antagonism of HIV-1 Nef to SERINC5 Particle Infectivity Restriction Involves the Counteraction of Virion-Associated Pools of the Restriction Factor.Journal of virology · 2016Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
A key function of the Nef protein of immunodeficiency viruses is the downregulation of the T-cell and macrophage coreceptor, CD4, from the surfaces of infected cells. CD4 downregulation depends on a conserved (D/E)XXXL(L/I)-type dileucine motif in the C-terminal, flexible loop of Nef, which mediates binding to the clathrin adaptor complexes AP-1, AP-2, and AP-3. We now report the identification of a consensus (D/E)D motif within this loop as a second, conserved determinant of interaction of Nef with AP-2, though not with AP-1 and AP-3. Mutations in this diacidic motif abrogate both AP-2 binding and CD4 downregulation. We also show that a dileucine motif from tyrosinase, both in its native context and in the context of Nef, can bind to AP-2 independently of a diacidic motif. These results thus identify a novel type of AP-2 interaction determinant, support the notion that AP-2 is the key clathrin adaptor for the downregulation of CD4 by Nef, and reveal a previously unrecognized diversity among dileucine sorting signals.
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Registered trials
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