Integrin adhesion receptors constitute a cell-signaling system whereby interactions in the small cytoplasmic domains of the heterodimeric α- and β-subunits provoke major functional alterations in the large extracellular domains. With two-dimensional NMR spectroscopy, we examined two synthetic peptides [αIIb(⁹⁸⁷MWKVGFFKRNR) and β3(⁷¹⁶KLLITIHDRKEFAKFEEERARAKWD)] encompassing the membrane-proximal regions of the cytoplasmic domain motifs from the platelet integrin complex αΙΙbβ3. These membrane-proximal regions contain two conserved motifs, represented by ⁹⁸⁹KVGFFKR in the αIIb-subunit, and ⁷¹⁶KLLITIHDR in the β3-subunit. The dimer interaction consists of two adjacent helices with residues V990 and F993 of the αΙΙb-subunit heavily implicated in the dimer interfacial region, as is I719 of β3. These residues are situated within the conserved motifs of their respective proteins. Further structural analysis of this unique peptide heterodimer suggests that two distinct conformers are present. The major structural difference between the two conformers is a bend in the β3-peptide between D723 and A728, whereas the helical character in the other regions remains intact. Earlier mutational analysis has shown that a salt bridge between the side chains of αΙΙb(R955) and β3(D723) is formed. When this ion pair was modeled into both conformers, increased nuclear Overhauser effect violations suggested that the more bent structure was less able to accommodate this interaction. These results provide a molecular level rationalization for previously reported biochemical studies, as well as a basis for an atomic level understanding of the intermolecular interactions that regulate integrin activity.