title: Localization and characterization of a heparin binding domain peptide of human von Willebrand factor.
abstract: Human von Willebrand factor, a plasma glycoprotein which plays a critical role in regulating hemostasis, binds heparin, but the physiological importance and mode of this interaction is poorly understood. Using the motif of an amino acid sequence of a consensus heparin binding synthetic peptide, a 23-residue sequence (Tyr565-Ala587) of human von Willebrand factor was identified that retains the consensus motif and binds heparin with affinity comparable with native von Willebrand factor and the consensus peptide. In a fluid phase binding assay, the Tyr565-Ala587 peptide competed effectively with von Willebrand factor for binding heparin. Synthesis and testing of peptides overlapping Tyr565-Ala587, as well as adjacent cationic regions, showed this core sequence to be the optimal linear binding domain. Far ultraviolet circular dichroism spectrometry of the Tyr565-Ala587 peptide suggested that the peptide undergoes conformational change upon binding heparin. The Tyr565-Ala587 peptide thus encompasses part (or all) of a functionally important heparin binding domain of von Willebrand factor. Further study of this and related peptides may be useful for exploring how heparin may influence von Willebrand factor-mediated platelet hemostasis.
authors.affiliation: Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
authors.forename: M
authors.initials: M
authors.lastname: Sobel
authors.forename: D F
authors.initials: DF
authors.lastname: Soler
authors.forename: J C
authors.initials: JC
authors.lastname: Kermode
authors.forename: R B
authors.initials: RB
authors.lastname: Harris
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D010455:Peptides / Q000378:metabolism*; D016415:Sequence Alignment; D013056:Spectrophotometry, Ultraviolet; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D010455:Peptides; D014841:von Willebrand Factor; D006493:Heparin