Molecular requirements for assembly and function of a minimized human integrin alpha(IIIb)beta(3)

Integrin subunit compatibility within and between species plays a major 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 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 beta(3) MIDAS domain. This allows us to express alpha(IIb)(1-233) and beta(3)(111-318) as a soluble, mini-integrin that retains RGD-dependent 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.