title: Identification of SVTCG in thrombospondin as the conformation-dependent, high affinity binding site for its receptor, CD36.
abstract: Thrombospondin (TSP) binds to its cellular receptor, CD36 (glycoprotein IV or IIIb), and participates in many adhesive cell interactions. We have shown that the CD36-TSP interaction occurs in a stepwise, conformation-dependent process. CD36 sequence 139-155 binds TSP and induces a second CD36-binding site, which binds CD36 sequence 93-110 with high affinity. To characterize this high affinity CD36-binding site on TSP, an anti-TSP monoclonal antibody (mAb), 7A-1e, was identified that showed augmentation of TSP binding in the presence of CD36 peptide P139-155. Purified mAb 7A-1e IgG specifically blocked both P139-155-augmented CD36 binding and P139-155-dependent CD36 peptide P93-110 binding to TSP, indicating that the binding sites on TSP for mAb 7A-1e and P93-110 are closely related. mAb 7A-1e IgG inhibited collagen-induced platelet aggregation in platelet-rich plasma. SVTCG is a cell adhesive motif in TSP. Both mAb 7A-1e and P93-110 specifically bound to a TSP peptide containing SVTCG, and the binding of mAb 7A-1e or P93-110 to TSP was inhibited by soluble SCTCG peptide. The SVTCG cell adhesive domain in TSP is the conformation-dependent, high affinity binding site for CD36 sequence 93-110.
authors.affiliation: Division of Hematology, Stanford University School of Medicine, California 94305.
authors.forename: W X
authors.initials: WX
authors.lastname: Li
authors.forename: R J
authors.initials: RJ
authors.lastname: Howard
authors.forename: L L
authors.initials: LL
authors.lastname: Leung
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D001665:Binding Sites; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D000939:Epitopes; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011487:Protein Conformation; D016024:Receptors, Cytoadhesin / Q000378:metabolism*; D019699:Thrombospondins
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D000939:Epitopes; D010980:Platelet Membrane Glycoproteins; D016024:Receptors, Cytoadhesin; D019699:Thrombospondins; D003094:Collagen