Molecular requirements for assembly and function of a minimized human integrin α(IIb)β₃

Integrin subunit compatibility within and between species plays a major role in heterodimer assembly and ligand specificity. As an example, human α(IIb) 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 α(IIb)(1-233) and β₃(111-318) as a soluble, mini-integrin that retains RGD-dependent ligand recognition. Thus, in the case of one integrin, α(IIb)β₃, the molecular requirements for integrin subunit compatibility and ligand recognition are intimately related.