High-Affinity α-Thrombin Binding to Platelet Glycoprotein Ibα: Identification of Two Binding Domains

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 14; pp. 6334 - 6338
• Main Authors: Gralnick, Harvey R., Williams, Sybil, McKeown, Laurie P., Hansmann, Kristin, Fenton, John W., Krutzsch, Henry
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 05-07-1994; National Acad Sciences
• Subjects: Amino Acid Sequence; Amino acids; Binding Sites; Blood Platelets - drug effects; Blood Platelets - physiology; Humans; Inhibitory concentration 50; Kinetics; Ligands; Molecular Sequence Data; Peptide Fragments - chemical synthesis; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Peptide Mapping; Peptides; Platelet activation; Platelet aggregation; Platelet Aggregation - drug effects; Platelet Membrane Glycoproteins - chemistry; Platelet Membrane Glycoproteins - metabolism; Platelets; Receptors; Structure-Activity Relationship; Thrombin - metabolism; Thrombin - pharmacology; Thrombin receptors; Thrombosis; Wasp Venoms - pharmacology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.14.6334

α-Thrombin binding to and activation of platelets are of major importance in the initiation of physiologic thrombi and in the genesis of arterial thrombus formation. We have studied the site(s) and affinity of thrombin binding to human platelets. Our studies of the peptide inhibition of thrombin binding indicate that the glycoprotein Ibα binding site is of high affinity, Kd≈ 10-10M, while the seven-transmembrane-domain site is a moderate-affinity thrombin binding site, Kd≈ 10-8M. Further studies to modulate the high- or moderate-affinity thrombin binding can be directed to a specific class of sites. This would allow partial or total inhibition of specific thrombin-platelet interaction(s) in different clinical settings.