Role of Fibrinogen α and γ Chain Sites in Platelet Aggregation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 22; pp. 10729 - 10732
• Main Authors: Farrell, David H., Thiagarajan, Perumal, Chung, Dominic W., Davie, Earl W.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.11.1992; National Acad Sciences
• Subjects: Aggregation; Amino Acid Sequence; Amino acids; Animals; Base Sequence; Biochemistry; Biological and medical sciences; Blood coagulation. Blood cells; Blood plasma; cell adhesion; Cell Line; Cell lines; characterization; fibrinogen; Fibrinogen - genetics; Fibrinogen - isolation & purification; Fibrinogen - metabolism; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods, hemostasis, fibrinolysis; Humans; Kinetics; Ligands; Macromolecular Substances; man; mediation; Molecular and cellular biology; Molecular Sequence Data; Molecular Weight; Mutagenesis, Site-Directed; Oligodeoxyribonucleotides; Platelet Aggregation; Platelet Membrane Glycoproteins - metabolism; Platelets; Plows; Receptors; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; requirements; Transfection; Aggregation; Human; Site specificity; Platelet; Gamma-Peptide chain; Integrin; Fibrinogen; Alpha-Peptide chain; Recombinant protein; Structure function relationship; Recognition; Biological receptor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.22.10729

Fibrinogen (Fbg) mediates platelet aggregation by its interaction with the platelet glycoprotein IIb-IIIa (integrin αIIbβ3). Peptides containing the amino acid sequence RGD derived from the α chain (residues α95-97 and residues α572-574) and the sequence HHLGGAKQAGDV derived from the carboxyl terminus of the γ chain of Fbg (residues γ400-411) inhibit these interactions. To determine the role of these sequences in intact Fbg, recombinant human Fbg (rFbg), mutant rFbgs with an RGD → RGE substitution at either position α97 or α574, and a rFbg γ'-containing variant that has a carboxyl-terminal interruption in the HHLGGAKQAGDV sequence have been expressed in transfected BHK cells. Purified rFbg and the two RGE mutant Fbgs were similar to plasma Fbg in platelet aggregation assays. In contrast, the γ' variant Fbg was markedly defective in platelet aggregation. These data support the proposals that the carboxyl-terminal region of the γ chain of Fbg is essential for optimal platelet aggregation and that the α-chain RGD sequences are neither necessary nor sufficient for platelet aggregation.