Identification of novel blood-borne soluble binding partners of factor H-related proteins

ABSTRACT: The deposition of circulating complement factor H-related (FHR) proteins in tissues around the body has been implicated in a series of complement-mediated diseases. However, the array of blood-borne binding partners with which they interact remains unclear. Here, we identify novel blood-borne binding partners of FHR proteins using untargeted immunoprecipitation and mass spectrometry. We uncover direct interactions between FHRs and soluble immune mediators including complement C4, cathepsin G (CTSG), mannose-binding lectin 2 (MBL2), platelet basic protein (PPBP), and fibrinogen-like protein 1 (FGL1). Functional assays show that FHR-1 and FHR-2 attenuate CTSG-mediated C3b degradation, while FHR-5 and FHL-1 appear to affect lectin pathway activation via MBL2 binding. These interactions suggest that FHRs perhaps confer activity not only through surface competition with factor H, but also via selective engagement with circulating ligands. Our findings expand the known FHR interactome and provide mechanistic insight into their accumulation at inflammatory sites within the ECM (extracellular matrix). This work reveals potential new avenues for understanding FHR biology and targeting complement dysregulation in disease.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

SUBMITTER: Tina Beyer  

LAB HEAD: Prof. Dr. Simon Clark

PROVIDER: PXD072296 | Pride | 2026-03-30

REPOSITORIES: Pride