Molecular requirements for assembly and function of a minimized human integrin alphaIIbbeta3.
Integrin subunit compatibility within and between species plays a major role in heterodimer assembly and ligand specificity. As an example, human alphaIIb pairs only with human beta3 and does not assemble a heterodimer with beta3 from other species. We use interspecies subunit chimeras to identify molecular requirements for subunit compatibility and show that species-restricted heterodimer assembly depends on a unique hexapeptide VGSDNH in an extended loop of the hypothetical human beta3 MIDAS domain. This allows us to express alphaIIb(1-233) and beta3(111-318) as a soluble, mini-integrin that retains RGD-dependent ligand recognition. Thus, in the case of one integrin, alphaIIbbeta3, the molecular requirements for integrin subunit compatibility and ligand recognition are intimately related.
McKay
B S
BS
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92017, USA.
Annis
D S
DS
Honda
S
S
Christie
D
D
Kunicki
T J
TJ
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry*; D006801:Humans; D039661:Integrin beta3; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry*; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins; D013045:Species Specificity; D013329:Structure-Activity Relationship
D015703:Antigens, CD; D039661:Integrin beta3; D046911:Macromolecular Substances; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C047981:arginyl-glycyl-aspartic acid