title: C1q-binding peptides share sequence similarity with C4 and induce complement activation.
abstract: Two peptide motifs that bind to C1q have been identified from phage displayed libraries. A first panning cycle recovered phage that displayed a [N/S]PFxL motif. A synthetic peptide with that motif blocked those phage from binding to C1q. A second panning cycle was conducted with the [N/S]PFxL motif peptide present, leading to recovery of phage displaying a different motif, SHY. The two motifs are specific for C1q and are competed by DNA and the cognate synthetic peptide but not by immunoglobulins. Phage displayed peptide sequences containing the [N/S]PFxL have significant sequence similarity to a region of complement component C4, suggesting a possible site of interaction between C4, or one of its processed forms, and C1q. The SHY motif peptide induces C4 consumption in a hemolytic assay, suggesting that it activates C1 independent of immune complexes. This peptide may activate C1 by a mechanism similar to the beta-amyloid peptides found in Alzheimer's disease.
authors.affiliation: Sackler Laboratory for Molecular Genetics and Informatics, Rockefeller University, 1230 York Ave, New York, NY 10021-6399, USA. bmessmer@nshs.edu
authors.forename: B T
authors.initials: BT
authors.lastname: Messmer
authors.forename: D S
authors.initials: DS
authors.lastname: Thaler
mesh_terms: D000818:Animals; D001435:Bacteriophages; D001665:Binding Sites; D001667:Binding, Competitive; D002352:Carrier Proteins; D003167:Complement Activation / Q000276:immunology*; D015922:Complement C1q / Q000378:metabolism*; D003181:Complement C4 / Q000737:chemistry*; D016208:Databases, Factual; D006168:Guinea Pigs; D006801:Humans; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020539:Sequence Analysis, Protein / Q000379:methods; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D003181:Complement C4; D019151:Peptide Library; D010455:Peptides; D011506:Proteins; C007105:c1q-binding proteins; D015922:Complement C1q