ArticleNature2016
A mechanism of viral immune evasion revealed by cryo-EM analysis of the TAP transporter.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 129 citations in OpenAlex.
- In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial.Nature medicine · 2022Trial
- Architectural principles of transporter-chaperone coupling within the native MHC I peptide-loading complex.Science advances · 2026Article
- The race between viral immune evasion and the MHC class I antigen processing pathway.FEMS microbiology reviews · 2026Review
- Alpha-herpesvirus US1 interacts with cGAS to suppress type I IFN responses and antiviral defense.PLoS pathogens · 2025Article
- Structurally diverse viral inhibitors converge on a shared mechanism to stall the antigen transporter TAP.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Structural Atlas of TAP Inhibition by Herpesviruses and Poxviruses.bioRxiv : the preprint server for biology · 2025Article
- Progress in skin gene therapy: From the inside and out.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Regulation of Granzymes A and B by High-Risk HPV: Impact on Immune Evasion and Carcinogenesis.Viruses · 2025Review
- Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2.Nature communications · 2025Article
- Identification of TAP2 protein variants resistant to inhibition by the HSV1 ICP47 protein.bioRxiv : the preprint server for biology · 2024Article
- Structure of a dimeric full-length ABC transporter.Nature communications · 2024Article
- Safety of non-replicative and oncolytic replication-selective HSV vectors.Trends in molecular medicine · 2024Review
- Inhibition and transport mechanisms of the ABC transporter hMRP5.Nature communications · 2024Article
- Principles of peptide selection by the transporter associated with antigen processing.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural basis for autoinhibition by the dephosphorylated regulatory domain of Ycf1.Nature communications · 2024Article
- Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection.iScience · 2024Article
- The expression and function of HSV ICP47 and its promoter in mice.Journal of virology · 2023Article
- A macrocyclic peptide inhibitor traps MRP1 in a catalytically incompetent conformation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Different routes of MHC-I delivery to phagosomes and their consequences to CD8 T cell immunity.Seminars in immunology · 2023Review
- The lysosomal transporter TAPL has a dual role as peptide translocator and phosphatidylserine floppase.Nature communications · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Cellular immunity against viral infection and tumour cells depends on antigen presentation by major histocompatibility complex class I (MHC I) molecules. Intracellular antigenic peptides are transported into the endoplasmic reticulum by the transporter associated with antigen processing (TAP) and then loaded onto the nascent MHC I molecules, which are exported to the cell surface and present peptides to the immune system. Cytotoxic T lymphocytes recognize non-self peptides and program the infected or malignant cells for apoptosis. Defects in TAP account for immunodeficiency and tumour development. To escape immune surveillance, some viruses have evolved strategies either to downregulate TAP expression or directly inhibit TAP activity. So far, neither the architecture of TAP nor the mechanism of viral inhibition has been elucidated at the structural level. Here we describe the cryo-electron microscopy structure of human TAP in complex with its inhibitor ICP47, a small protein produced by the herpes simplex virus I. Here we show that the 12 transmembrane helices and 2 cytosolic nucleotide-binding domains of the transporter adopt an inward-facing conformation with the two nucleotide-binding domains separated. The viral inhibitor ICP47 forms a long helical hairpin, which plugs the translocation pathway of TAP from the cytoplasmic side. Association of ICP47 precludes substrate binding and prevents nucleotide-binding domain closure necessary for ATP hydrolysis. This work illustrates a striking example of immune evasion by persistent viruses. By blocking viral antigens from entering the endoplasmic reticulum, herpes simplex virus is hidden from cytotoxic T lymphocytes, which may contribute to establishing a lifelong infection in the host.
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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.