ArticleProceedings of the National Academy of Sciences of the United States of America2022
Structure of PLA2R reveals presentation of the dominant membranous nephropathy epitope and an immunogenic patch.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 25 citations in OpenAlex.
- Treatment strategies for rituximab-resistant primary membranous nephropathy: from resistance mechanisms to emerging therapies.Frontiers in immunology · 2026Review
- Immunotherapy of membranous nephropathy: strategic evolution from CD20 monoclonal antibodies to future vaccines.Frontiers in immunology · 2026Review
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Detection and prognostic relevance of PLA2R epitopes in idiopathic membranous nephropathy: a simultaneous quantitative multiplex suspension array detection method.Clinical kidney journal · 2025Article
- Autoimmune diseases: targets, biology, and drug discovery.Acta pharmacologica Sinica · 2024Review
- Organelle resolved proteomics uncovers PLA2R1 as a novel cell surface marker required for chordoma growth.Acta neuropathologica communications · 2024Article
- Bi-specific autoantigen-T cell engagers as targeted immunotherapy for autoreactive B cell depletion in autoimmune diseases.Frontiers in immunology · 2024Article
- NELL1 membranous nephropathy: clinical associations provide mechanistic clues.Frontiers in nephrology · 2024Review
- Structure of PLA2R reveals presentation of the dominant membranous nephropathy epitope and an immunogenic patch.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Membranous nephropathy is an autoimmune kidney disease caused by autoantibodies targeting antigens present on glomerular podocytes, instigating a cascade leading to glomerular injury. The most prevalent circulating autoantibodies in membranous nephropathy are against phospholipase A2 receptor (PLA2R), a cell surface receptor. The dominant epitope in PLA2R is located within the cysteine-rich domain, yet high-resolution structure-based mapping is lacking. In this study, we define the key nonredundant amino acids in the dominant epitope of PLA2R involved in autoantibody binding. We further describe two essential regions within the dominant epitope and spacer requirements for a synthetic peptide of the epitope for drug discovery. In addition, using cryo-electron microscopy, we have determined the high-resolution structure of PLA2R to 3.4 Å resolution, which shows that the dominant epitope and key residues within the cysteine-rich domain are accessible at the cell surface. In addition, the structure of PLA2R not only suggests a different orientation of domains but also implicates a unique immunogenic signature in PLA2R responsible for inducing autoantibody formation and recognition.
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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.