Molecular requirements for assembly and function of a minimized human integrin alphaIIbbeta3

Abstract Integrin subunit compatibility within and between species plays a major role in heterodimer assembly and ligand specificity. As an example, human αIIb pairs only with human β3 and does not assemble a heterodimer with β3 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 β3 MIDAS domain. This allows us to express αIIb(1-233) and β3(111-318) as a soluble, mini-integrin that retains RGD-dependent ligand recognition. Thus, in the case of one integrin, αIIbβ3, the molecular requirements for integrin subunit compatibility and ligand recognition are intimately related.