9IGO

PR3 S203A I221N W222N G223T mutant in complex with the extracellular domain of CD177

Summary for 9IGO

• Entry DOI: 10.2210/pdb9igo/pdb
• Descriptor: Myeloblastin, CD177 antigen, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: serine protease, anca-antigen, cd177 receptor, surface proteins, glycoproteins, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 49177.23

Authors

Zheng-Gerard, C.,El Omari, K.,Seiradake, E. (deposition date: 2025-02-19, release date: 2026-02-25, Last modification date: 2026-03-04)

Primary citation

Zheng-Gerard, C.,Joha, J.,Carrasquero, M.,El Omari, K.,Lowe, E.,Dubey, S.,Draper, S.J.,Chang, Y.C.,Lin, H.H.,Salama, A.D.,McHugh, K.,Seiradake, E.
Structures of proteinase 3 and the CD177 receptor complex reveal a major autoantibody epitope.
Embo Rep., 2026

PubMed Abstract: 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.

PubMed: 41703070
DOI: 10.1038/s44319-026-00716-5

Experimental method

X-RAY DIFFRACTION (1.5 Å)