MOLECULAR REQUIREMENTS FOR ASSEMBLY AND FUNCTION OF A MINIMIZED HUMANINTEGRIN ALPHA(IIIB)BETA(3)

Integrin subunit compatibility within and between species plays a majo r role in heterodimer assembly and ligand specificity. As an example, human alpha(IIb) pairs only with human beta(3) and does not assemble a heterodimer with beta(3) from other species. We use interspecies subu nit chimeras to identify molecular requirements for subunit compatibil ity and show that species-restricted heterodimer assembly depends on a unique hexapeptide VGSDNH in an extended loop of the hypothetical hum an beta(3) MIDAS domain. This allows us to express alpha(IIb)(1-233) a nd beta(3)(111-318) as a soluble, mini-integrin that retains RGD-depen dent ligand recognition. Thus, in the case of one integrin, alpha(IIb) beta(3), the molecular requirements for integrin subunit compatibility and ligand recognition are intimately related.