Structural comparison of αIIbβ3 by itself and in complex with the fibrinogen γC peptide and the R6H8 Fab, showing the ligand-mimetic binding of the R6H8 Fab. Atomic models of αIIbβ3 in complex with fibrinogen γC peptide (top), αIIbβ3-R6H8 Fab complex (middle), and apo αIIbβ3 (bottom). Each structure is colored based on individual subunits. The angles between the βI and hybrid domains in the 3 structures are indicated. Each inset shows the detailed interactions in the RGD-binding pocket. The pink asterisk indicates that D106 from the CDR3 of R6H8 Fab heavy chain and D410 from the fibrinogen γC peptide both directly coordinate the MIDAS Mg²⁺ by replacing the water molecule in the apo structure. The yellow asterisk indicates that S123 from the βI domain interacts with MIDAS Mg²⁺ directly in the fully extended conformation, whereas in the apo state, S123 interacts with the MIDAS Mg²⁺ via a water bridge. The green asterisk indicates that the dramatic change in orientation of the S126 side chain induced by R6H8 Fab binding as a result of its interaction with R6H8 Fab D108 (CDR3 heavy chain) and Y32 (CDR1 light chain) leads to loss of the ADMIDAS Ca²⁺ (dotted sphere). The red asterisk indicates that the loss of the ADMIDAS Ca²⁺ results in loss of its interaction with M335’s backbone carbonyl, which leads to swing-out of the hybrid domain. Residues involved in binding the synergistic metal ion binding site Ca²⁺ (yellow sphere), MIDAS Mg²⁺ (gold sphere), and ADMIDAS Ca²⁺ (yellow sphere) are shown as sticks. Interactions in synergistic metal ion binding site, MIDAS, and ADMIDAS regions are indicated with dotted purple lines. Charge interactions are indicated with dotted red lines, whereas hydrogen bonds are indicated with dotted black lines. The distances between the M335 carbonyl and the ADMIDAS Ca²⁺ are indicated. PDB, Protein Data Bank.