ArticleCell host & microbe2019
Structural Basis for Tetherin Antagonism as a Barrier to Zoonotic Lentiviral Transmission.
Article in Cell host & microbe, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- Ancestral reconstruction supports that loss of Nef-mediated T cell modulation coincided with the emergence of pathogenic lentiviruses.Journal of virology · 2025Article
- HIV-1 Nef Uses a Conserved Pocket to Recruit the N-Terminal Cytoplasmic Tail of Serinc3.Viruses · 2025Article
- HIV-2 evades restriction by ZAP through adaptations in the U3 LTR region despite increased CpG levels.Nucleic acids research · 2025Article
- Adaptor Protein Complexes in HIV-1 Pathogenesis: Mechanisms and Therapeutic Potential.Viruses · 2025Review
- Kinetic investigation reveals an HIV-1 Nef-dependent increase in AP-2 recruitment and productivity at endocytic sites.Molecular biology of the cell · 2024Article
- Phylogenetic Reconstruction and Functional Characterization of the Ancestral Nef Protein of Primate Lentiviruses.Molecular biology and evolution · 2023Article
- Substitutions in Nef That Uncouple Tetherin and SERINC5 Antagonism Impair Simian Immunodeficiency Virus Replication in Primary Rhesus Macaque Lymphocytes.Journal of virology · 2022Article
- Bone marrow stromal cell antigen 2(BST2) suppresses the migration and invasion of trophoblasts in preeclampsia by downregulating matrix metallopeptidase 2(MMP2).Bioengineered · 2022Article
- Simian Immunodeficiency Virus SIVgsn-99CM71 Vpu Employs Different Amino Acids To Antagonize Human and Greater Spot-Nosed Monkey BST-2.Journal of virology · 2022Article
- Reconstituting and Purifying Assembly Intermediates of Clathrin Adaptors AP1 and AP2.Methods in molecular biology (Clifton, N.J.) · 2022Article
- An Amino Acid Polymorphism within the HIV-1 Nef Dileucine Motif Functionally Uncouples Cell Surface CD4 and SERINC5 Downregulation.Journal of virology · 2021Article
- Selective Disruption of SERINC5 Antagonism by Nef Impairs SIV Replication in Primary CD4Journal of virology · 2021Article
- Profile of James H. Hurley.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Review
- Retroviral Restriction Factors and Their Viral Targets: Restriction Strategies and Evolutionary Adaptations.Microorganisms · 2020Review
- Nef homodimers down-regulate SERINC5 by AP-2-mediated endocytosis to promote HIV-1 infectivity.The Journal of biological chemistry · 2020Article
- Complementarity of Hydrogen/Deuterium Exchange Mass Spectrometry and Cryo-Electron Microscopy.Trends in biochemical sciences · 2020Review
- Structural basis of CD4 downregulation by HIV-1 Nef.Nature structural & molecular biology · 2020Article
- Editorial overview: Membrane traffic in the time of COVID-19.Current opinion in cell biology · 2020Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Tetherin is a host defense factor that physically prevents virion release from the plasma membrane. The Nef accessory protein of simian immunodeficiency virus (SIV) engages the clathrin adaptor AP-2 to downregulate tetherin via its DIWK motif. As human tetherin lacks DIWK, antagonism of tetherin by Nef is a barrier to simian-human transmission of non-human primate lentiviruses. To determine the molecular basis for tetherin counteraction, we reconstituted the AP-2 complex with a simian tetherin and SIV Nef and determined its structure by cryoelectron microscopy (cryo-EM). Nef refolds the first α-helix of the β2 subunit of AP-2 to a β hairpin, creating a binding site for the DIWK sequence. The tetherin binding site in Nef is distinct from those of most other Nef substrates, including MHC class I, CD3, and CD4 but overlaps with the site for the restriction factor SERINC5. This structure explains the dependence of SIVs on tetherin DIWK and consequent barrier to human transmission.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.