title: Binding of cystatin C to C4: the importance of sense-antisense peptides in their interaction.
abstract: Hydropathic anticomplementarity of amino acids indicates that peptides derived from complementary DNA strands may form amphiphilic structures and bind one another. By using this concept, we have found that the antisense peptide Ser-Tyr-Asp-Leu complementary to the segment Gln-Ile-Val-Ala-Gly (residues 55-59) in cystatin C (an inhibitor of cysteine proteases) is located at positions 611-614 of the beta chain of human C4, the fourth component of complement. Here we describe and characterize the specific interaction between cystatin C and C4 by ligand affinity chromatography and ELISA. Interaction between the two native proteins was mimicked on replacement of one of them with the corresponding sense-antisense peptide coupled to a carrier protein, and the binding was inhibited by these synthetic peptides in solution. Through the interaction with C4, cystatin C may play a regulatory role in complement activation that might be of particular importance at tissue sites where both proteins are produced by macrophages.
authors.affiliation: Department of Pathology, New York University Medical Center, NY 10016.
authors.forename: J
authors.initials: J
authors.lastname: Ghiso
authors.forename: E
authors.initials: E
authors.lastname: Saball
authors.forename: J
authors.initials: J
authors.lastname: Leoni
authors.forename: A
authors.initials: A
authors.lastname: Rostagno
authors.forename: B
authors.initials: B
authors.lastname: Frangione
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002556:Cerebrospinal Fluid Proteins / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism*; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D009994:Osmolar Concentration; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: C525030:CST3 protein, human; D002556:Cerebrospinal Fluid Proteins; D003181:Complement C4; D055316:Cystatin C; D015891:Cystatins; D009842:Oligopeptides; D010455:Peptides