ArticleThe Journal of biological chemistry2014
Combined effects of ankylosing spondylitis-associated ERAP1 polymorphisms outside the catalytic and peptide-binding sites on the processing of natural HLA-B27 ligands.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Rewiring tumor visibility: The immunopeptidome as a dynamic interface between antigen processing, microenvironmental stress, and immune recognition.Frontiers in oncology · 2025Review
- Breaking boundaries in ankylosing spondylitis: how innovative cell therapies reshape immunity, drive cutting-edge advances, and face future challenges.Frontiers in immunology · 2025Review
- Autoimmune alleles at the major histocompatibility locus modify melanoma susceptibility.American journal of human genetics · 2023Article
- FunctionalCells · 2022Article
- The ER Aminopeptidases, ERAP1 and ERAP2, synergize to self-modulate their respective activities.Frontiers in immunology · 2022Article
- Know thy immune self and non-self: Proteomics informs on the expanse of self and non-self, and how and where they arise.Proteomics · 2021Review
- Spondyloarthritis and the Human Leukocyte Antigen (HLA)-BFrontiers in immunology · 2021Review
- Review
- Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis.Molecular & cellular proteomics : MCP · 2019Article
- Redundancy and Complementarity between ERAP1 and ERAP2 Revealed by their Effects on the Behcet's Disease-associated HLA-B*51 Peptidome.Molecular & cellular proteomics : MCP · 2019Article
- The role of polymorphic ERAP1 in autoinflammatory disease.Bioscience reports · 2018Review
- An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes.Scientific reports · 2018Article
- Ranking the Contribution of Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphisms to Shaping the HLA-B*27 Peptidome.Molecular & cellular proteomics : MCP · 2018Article
- How ERAP1 and ERAP2 Shape the Peptidomes of Disease-Associated MHC-I Proteins.Frontiers in immunology · 2018Review
- RUNX3 and T-Bet in Immunopathogenesis of Ankylosing Spondylitis-Novel Targets for Therapy?Frontiers in immunology · 2018Review
- The interplay between HLA-B27 and ERAP1/ERAP2 aminopeptidases: from anti-viral protection to spondyloarthritis.Clinical and experimental immunology · 2017Review
- The Behçet's disease-associated variant of the aminopeptidase ERAP1 shapes a low-affinity HLA-B*51 peptidome by differential subpeptidome processing.The Journal of biological chemistry · 2017Article
- Both rare and common ERAP1 allotypes have distinct functionality defined by polymorphic context and are important in AS association.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Connecting genetic risk to disease end points through the human blood plasma proteome.Nature communications · 2017Article
- The Role of Conformational Dynamics in Antigen Trimming by Intracellular Aminopeptidases.Frontiers in immunology · 2017Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ERAP1 polymorphism involving residues 528 and 575/725 is associated with ankylosing spondylitis among HLA-B27-positive individuals. We used four recombinant variants to address the combined effects of the K528R and D575N polymorphism on the processing of HLA-B27 ligands. The hydrolysis of a fluorogenic substrate, Arg-528/Asp-575 < Lys-528/Asp-575 < Arg-528/Asn-575 < Lys-528/Asn-575, indicated that the relative activity of variants carrying Arg-528 or Lys-528 depends on residue 575. Asp-575 conferred lower activity than Asn-575, but the difference depended on residue 528. The same hierarchy was observed with synthetic precursors of HLA-B27 ligands, but the effects were peptide-dependent. Sometimes the epitope yields were variant-specific at all times. For other peptides, concomitant generation and destruction led to similar epitope amounts with all the variants at long, but not at short, digestion times. The generation/destruction balance of two related HLA-B27 ligands was analyzed in vitro and in live cells. Their relative yields at long digestion times were comparable with those from HLA-B27-positive cells, suggesting that ERAP1 was a major determinant of the abundance of these peptides in vivo. The hydrolysis of fluorogenic and peptide substrates by an HLA-B27 ligand or a shorter peptide, respectively, was increasingly inhibited as a function of ERAP1 activity, indicating that residues 528 and 575 affect substrate inhibition of ERAP1 trimming. The significant and complex effects of co-occurring ERAP1 polymorphisms on multiple HLA-B27 ligands, and their potential to alter the immunological and pathogenetic features of HLA-B27 as a function of the ERAP1 context, explain the epistatic association of both molecules in ankylosing spondylitis.
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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.