ArticleNature structural & molecular biology2020
Structural basis of CD4 downregulation by HIV-1 Nef.
Article in Nature structural & molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- CCDC32 collaborates with the membrane to assemble the AP-2 clathrin adaptor complex.Science advances · 2026Article
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- HIV-2 infection as a comparative lens for functional HIV-1 remission.Frontiers in immunology · 2026Review
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 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
- Restriction of HIV-1 infectivity by interferon and IFITM3 is counteracted by Nef.Science advances · 2025Article
- Multifaceted Role of Nef in HIV-Associated Neurocognitive Disorder: Histopathological Alterations and Underlying Mechanisms.Brain sciences · 2025Review
- Article
- Adaptor Protein Complexes in HIV-1 Pathogenesis: Mechanisms and Therapeutic Potential.Viruses · 2025Review
- PD-1 suppression enhances HIV reactivation and T-cell immunity via MAPK/NF-κB signaling.European journal of medical research · 2025Article
- Host Subcellular Organelles: Targets of Viral Manipulation.International journal of molecular sciences · 2024Review
- Kinetic investigation reveals an HIV-1 Nef-dependent increase in AP-2 recruitment and productivity at endocytic sites.Molecular biology of the cell · 2024Article
- HIV-1 subtypes maintain distinctive physicochemical signatures in Nef domains associated with immunoregulation.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2023Article
- Integrative structure determination of histones H3 and H4 using genetic interactions.The FEBS journal · 2023Article
- Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs.Nature communications · 2023Article
- Article
- Article
- Nef enhances HIV-1 replication and infectivity independently of SERINC5 in CEM T cells.Virology · 2023Article
- Impact ofFrontiers in microbiology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
The HIV-1 Nef protein suppresses multiple immune surveillance mechanisms to promote viral pathogenesis and is an attractive target for the development of novel therapeutics. A key function of Nef is to remove the CD4 receptor from the cell surface by hijacking clathrin- and adaptor protein complex 2 (AP2)-dependent endocytosis. However, exactly how Nef does this has been elusive. Here, we describe the underlying mechanism as revealed by a 3.0-Å crystal structure of a fusion protein comprising Nef and the cytoplasmic domain of CD4 bound to the tetrameric AP2 complex. An intricate combination of conformational changes occurs in both Nef and AP2 to enable CD4 binding and downregulation. A pocket on Nef previously identified as crucial for recruiting class I MHC is also responsible for recruiting CD4, revealing a potential approach to inhibit two of Nef's activities and sensitize the virus to immune clearance.
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Registered trials
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.