Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/81790
Type: Journal article
Title: Identification of a second heparin binding domain in human complement factor H
Author: Blackmore, T.
Hellwage, J.
Sadlon, T.
Higgs, N.
Zipfel, P.
Ward, H.
Gordon, D.
Citation: Journal of Immunology, 1998; 160(7):3342-3348
Publisher: AMER ASSOC IMMUNOLOGISTS
Issue Date: 1998
ISSN: 0022-1767
1550-6606
Statement of
Responsibility: 
Timothy K. Blackmore, Jens Hellwage, Tania A. Sadlon, Naomi Higgs, Peter F. Zipfel, Helena M. Ward, and David L. Gordon
Abstract: Complement 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.
Keywords: Humans; Heparin; Apolipoproteins; Blood Proteins; Complement Factor H; Recombinant Proteins; Sequence Deletion; Binding Sites; Repetitive Sequences, Nucleic Acid; Consensus Sequence; Protein Structure, Tertiary
Rights: Copyright © 1998 by The American Association of Immunologists
RMID: 0030000220
Published version: http://www.jimmunol.org/content/160/7/3342.abstract
Appears in Collections:Medical Education Unit publications

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