The platelet integrin alphaIIbbeta3 binds to the RGD and AGD motifs in fibrinogen.
Fibrinogen (Fbg) mediates platelet aggregation by binding the alphaIIbbeta3 integrin receptor, but the interaction of the receptor with peptide motifs of Fbg remains unresolved. This paper describes the use of self-assembled monolayers (SAMs) to study the adhesion of alphaIIbbeta3-transfected CHO cells to the GRGDS and HHLGGAKQAGDV motifs within Fbg. Cells adhered to and spread on monolayers presenting either peptide. Cell adhesion could be inhibited by either soluble peptide, demonstrating that the peptides bind competitively to the integrin. A peptide array was used to show that AGD was the minimal binding sequence in HHLGGAKQAGDV and that the receptor recognizes ligands of the form GXGDSC, where X is a hydrophobic or basic residue. This work revises our understanding of the alphaIIbbeta3 specificity and also suggests a new class of antithrombotic agents.
Department of Chemistry and Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Juan
J
Sánchez-Cortés
Milan
M
Mrksich
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002448:Cell Adhesion; D006224:Cricetinae; D003412:Cricetulus; D005340:Fibrinogen / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs
D005343:Fibrinolytic Agents; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen