Molecular mechanism of A:a knob-hole bond rupture. Conformational transitions and remodeling of the A:a binding interface are exemplified for single-point mutants γK356Q (green balls) and γD297N (red balls), which result in kinetic partitioning into the bi-phasic catch-slip-type (A) and slip-type bond rupture pathways (B). The atomic structure of the A:a knob-hole complex (in ribbon representation) showing knob A (residues α17-36; in orange color) and hole a with the interior region (γ335-365; in green), loop I (γ315-330; in blue), and movable flap (γ295-305; in red). The pulling force is applied to residue α36 in knob A (small arrows), whereas residue γ159 in the γ-nodule is constrained (color denotation as in Figure 6).