Peptide ligands for integrin alpha v beta 3 selected from random phage display libraries.
The integrin alpha v beta 3 binds promiscuously to cell-adhesive proteins: vitronectin, fibronectin, and several others containing the RGD motif. We have explored molecular recognition by alpha v beta 3 through selection of ligands from large random libraries of peptides displayed on phage. Ligands bound by alpha beta 3 consisted primarily of RGD peptides; however, these peptides showed considerable heterogeneity with respect to the identities of amino acids flanking RGD. The tolerance of alpha v beta 3 for RGD peptides of diverse composition is consistent with its role in vivo as a versatile receptor for RGD-containing extracellular matrix proteins. Peptide ligands for alpha v beta 3 also included a novel binding sequence, identical to a tetrapeptide found in vitronectin, which is a candidate for a synergistic site in this adhesive protein that may act in concert with RGD to promote molecular recognition.
Healy
J M
JM
Protein Engineering Research Institute, Osaka, Japan.
Murayama
O
O
Maeda
T
T
Yoshino
K
K
Sekiguchi
K
K
Kikuchi
M
M
D000595:Amino Acid Sequence; D001435:Bacteriophages; D001483:Base Sequence; D017931:DNA Primers; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D016023:Integrins / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011485:Protein Binding; D011897:Random Allocation; D016024:Receptors, Cytoadhesin / Q000302:isolation & purification / Q000378:metabolism*; D019030:Receptors, Vitronectin; D013329:Structure-Activity Relationship; D013698:Templates, Genetic
D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D016023:Integrins; D009842:Oligopeptides; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; C047981:arginyl-glycyl-aspartic acid