title: Human serum amyloid P component oligomers bind and activate the classical complement pathway via residues 14-26 and 76-92 of the A chain collagen-like region of C1q.
abstract: Serum amyloid P component (SAP) was polymerized using the cleavable cross-linker 3,3'-dithio-bis-(sulfo-succinimidylpropionate) to study its interaction with the C system. Dimers and trimers, but no larger oligomers, were observed; the trimers retained native SAP immunoreactivity (except for one calcium-dependent epitope) without displaying neo-SAP epitopes. The SAP trimers bound strongly to C1q, at the level of the collagen-like region (CLR). SAP bound to synthetic C1q A chain peptides 14-26 and 76-92, and these peptides inhibited the binding of SAP trimers to the CLR. When incubated in dilute human serum, SAP trimers consumed total C and C4, but not alternative pathway, hemolytic activities. Consumption of C4 by SAP trimers was inhibited by C1q A chain peptide 14-26. Thus, SAP oligomers bind C1q and activate the classical C pathway via the collagen-like region of C1q, at sites located within residues 14-26 and/or 76-92 of the C1q A chain.
authors.affiliation: Department of Immunology/Microbiology, Rush Medical College, Chicago, IL 60612.
authors.forename: S C
authors.initials: SC
authors.lastname: Ying
authors.forename: A T
authors.initials: AT
authors.lastname: Gewurz
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: H
authors.initials: H
authors.lastname: Gewurz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D003094:Collagen / Q000737:chemistry*; D015922:Complement C1q / Q000737:chemistry* / Q000502:physiology*; D003171:Complement Pathway, Classical / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D000683:Serum Amyloid P-Component / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000683:Serum Amyloid P-Component; D015922:Complement C1q; D003094:Collagen