The amino-terminal one-third of alpha IIb defines the ligand recognition specificity of integrin alpha IIb beta 3.
The integrin alpha subunits play a major role in the regulation of ligand binding specificity. To gain further insight into the regions of the alpha subunits that regulate ligand specificity, we have utilized alpha v / alpha IIb chimeras to identify regions of alpha IIb that when substituted for the homologous regions of alpha v switched the ligand binding phenotype of alpha v beta 3 to that of alpha IIb beta 3. We report that the ligand recognition specificity of beta 3 integrins is regulated by the amino-terminal one-third of the alpha subunit. Substitution of the amino-terminal portion of alpha v with the corresponding 334 residues of alpha IIb reconstituted reactivity with both alpha IIb beta 3-specific activation-dependent (PAC1) and -independent (OPG2) ligand mimetic antibodies in addition to small highly specific activation-independent ligands. In contrast, substitution of the amino-terminal portion alone or the divalent cation repeats alone were not sufficient to change ligand binding specificity. These data in combination with previous studies demonstrate that integrin ligand recognition requires cooperation between elements in both the alpha and beta subunits and indicate that the ligand binding pocket is a structure assembled from elements of both the alpha and beta subunits.
Loftus
J C
JC
Department of Vascular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Halloran
C E
CE
Ginsberg
M H
MH
Feigen
L P
LP
Zablocki
J A
JA
Smith
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D005340:Fibrinogen / Q000737:chemistry; D008024:Ligands; D008969:Molecular Sequence Data; D009842:Oligopeptides; D010455:Peptides / Q000737:chemistry; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D014162:Transfection
D008024:Ligands; D009842:Oligopeptides; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011993:Recombinant Fusion Proteins; C027539:fibrinopeptides gamma; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen