Academic Journal
Structures of proteinase 3 and the CD177 receptor complex reveal a major autoantibody epitope
| Τίτλος: | Structures of proteinase 3 and the CD177 receptor complex reveal a major autoantibody epitope |
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| Συγγραφείς: | Zheng-Gérard, C, Joha, J, Carrasquero, M, El Omari, K, Lowe, E, Dubey, S, Draper, SJ, Chang, Y-C, Lin, H-H, Salama, AD, McHugh, K, Seiradake, E |
| Στοιχεία εκδότη: | Springer Nature |
| Έτος έκδοσης: | 2026 |
| Συλλογή: | Oxford University Research Archive (ORA) |
| Περιγραφή: | Granulomatosis with polyangiitis is a life-threatening systemic vasculitis, characterised by anti-neutrophil cytoplasmic autoantibodies (ANCA) most commonly against proteinase 3 (PR3), a protease expressed intracellularly and on the surface of neutrophils. Most cell surface PR3 is bound to the receptor CD177; however, the molecular mechanism of the interactions is not well understood. Here, we present crystal structures of CD177 in complex with PR3 and unliganded CD177. We describe a mainly hydrophobic binding interface between PR3 and CD177, involving the first two Ly6/uPAR (LU) domains of CD177. These form a globular structure which is connected to downstream domains via a flexible linker. Using a panel of PR3-ANCA-positive patient samples, we show that a significant proportion of ANCAs target the CD177-binding site of PR3 in these samples. Structure-guided mutation of the CD177-binding site on PR3 is effective in reducing PR3-ANCA binding. The results demonstrate that the CD177-binding surface of PR3 harbours a major PR3-ANCA epitope, and that the extent of binding to this surface varies between different patients. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Γλώσσα: | English |
| DOI: | 10.1038/s44319-026-00716-5 |
| Διαθεσιμότητα: | https://doi.org/10.1038/s44319-026-00716-5 https://ora.ox.ac.uk/objects/uuid:85fa0e6b-2634-4608-b4ef-f1cb5a923585 |
| Rights: | info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Αριθμός Καταχώρησης: | edsbas.1FC085DF |
| Βάση Δεδομένων: | BASE |
| DOI: | 10.1038/s44319-026-00716-5 |
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