{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:48:57Z","timestamp":1791276537981,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2006,3,27]],"date-time":"2006-03-27T00:00:00Z","timestamp":1143417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,3,27]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The complement inhibitor Factor H has three distinct binding sites for C3b and for heparin, but in solution uses specifically the most C-terminal domain, i.e. short consensus repeats (SCR) 20 for ligand interaction. Two novel monoclonal antibodies (mABs C14 and C18) that bind to the most C-terminal domain SCR 20 completely blocked interaction of Factor H with the ligands C3b, C3d, heparin and binding to endothelial cells. In contrast, several mAbs that bind to the N-terminus and to the middle regions of the molecule showed no or minor inhibitory effects when assayed by enzyme-linked immunosorbent assay (ELISA) and ligand interaction assays. This paradox between a single functional binding site identified for native Factor H versus multiple interaction sites reported for deletion constructs is explained by a compact conformation of the fluid phase protein with one accessible binding site. On zymosan particles mAbs C14 and C18 blocked alternative pathway activation completely. Thus demonstrating that native Factor H makes the first and initial contact with the C terminus, which is followed by N terminally mediated complement regulation. These results are explained by a conformational hypothetical model: the native Factor H protein has a compact structure and only one binding site accessible. Upon the first contact the protein unfolds and exposes the additional binding sites. This model does explain how Factor H mediates recognition functions during complement control and the clustering of disease associated mutations in patients with haemolytic uraemic syndrome that have been reported in the C-terminal recognition domain of Factor H.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2006.03071.x","type":"journal-article","created":{"date-parts":[[2006,3,27]],"date-time":"2006-03-27T22:53:29Z","timestamp":1143500009000},"page":"342-352","source":"Crossref","is-referenced-by-count":123,"title":["The C-terminus of complement regulator Factor H mediates target recognition: evidence for a compact conformation of the native protein"],"prefix":"10.1093","volume":"144","author":[{"given":"M","family":"Oppermann","sequence":"first","affiliation":[{"name":"Department of Immunology, University of G\u00f6ttingen, G\u00f6ttingen, 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