Identification of a second heparin binding domain in human complement factor H

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dc.contributor.authorBlackmore, T.
dc.contributor.authorHellwage, J.
dc.contributor.authorSadlon, T.
dc.contributor.authorHiggs, N.
dc.contributor.authorZipfel, P.
dc.contributor.authorWard, H.
dc.contributor.authorGordon, D.
dc.date.issued1998
dc.description.abstractComplement factor H (fH) regulates activation of the alternative pathway of C, reducing the amount of C3b deposited on sialic acid-rich surfaces. Heparin binding has been used as a model for examining the sialic acid- binding characteristics of fH. We have previously shown thai of the 20 short consensus repeat (SCR) modules of fH, SCR 7 contains an important heparin binding site, but other SCRs also play a role in heparin binding. To localize the other sites, we prepared recombinant truncated and SCR deletion mutants of fH and tested them by heparin-agarose affinity chromatography. The 5 C- terminal SCRs were found to contain a heparin binding site as an SCR 7 deletion mutant of the N terminal 15 SCRs did not bind heparin, but a construct consisting of SCRs 16-20 was shown to bind heparin. Double deletion of SCRs 7 and 20 fH abrogated binding to heparin, indicating that SCR 20 contains a heparin binding site. This finding was confirmed with the observation that attachment of SCR 20 to a group of nonbinding SCRs produced a heparin-binding protein. A protein consisting of SCRs 19 and 20 did not bind heparin, whereas SCRs 18-20 did, indicating that, although SCR 20 contains a heparin binding site, at least two nonspecific adjacent SCRs are required. fH-related protein-3 (FHR-3) possesses an SCR homologous to SCR 7 of fH and bound heparin, whereas FHR-4, which lacks such an SCR, did not. Thus, fH contains two separate heparin binding sites which are located in SCRs 7 and 20.
dc.description.statementofresponsibilityTimothy K. Blackmore, Jens Hellwage, Tania A. Sadlon, Naomi Higgs, Peter F. Zipfel, Helena M. Ward, and David L. Gordon
dc.identifier.citationJournal of Immunology, 1998; 160(7):3342-3348
dc.identifier.doi10.4049/jimmunol.160.7.3342
dc.identifier.issn0022-1767
dc.identifier.issn1550-6606
dc.identifier.orcidWard, H. [0000-0002-3831-1205]
dc.identifier.urihttp://hdl.handle.net/2440/81790
dc.language.isoen
dc.publisherOXFORD UNIV PRESS
dc.rightsCopyright © 1998 by The American Association of Immunologists
dc.source.urihttp://www.jimmunol.org/content/160/7/3342.abstract
dc.subjectHumans
dc.subjectHeparin
dc.subjectApolipoproteins
dc.subjectBlood Proteins
dc.subjectComplement Factor H
dc.subjectRecombinant Proteins
dc.subjectSequence Deletion
dc.subjectBinding Sites
dc.subjectRepetitive Sequences, Nucleic Acid
dc.subjectConsensus Sequence
dc.subjectProtein Structure, Tertiary
dc.titleIdentification of a second heparin binding domain in human complement factor H
dc.typeJournal article
pubs.publication-statusPublished

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