Structures of proteinase 3 and the CD177 receptor complex reveal a major autoantibody epitope

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

SUBMITTER: Céline Zheng-Gérard 

PROVIDER: S-SCDT-10_1038-S44319-026-00716-5 | biostudies-other |

REPOSITORIES: biostudies-other