Fig. 6

Structural insights into the enhanced pH-dependent interaction of the YML Fc variant. a Superimposed complex model structures of hFcRn/YML and hFcRn/wild-type Fc, illustrating the conformational differences. The hFcRn α-chain, β2-microglobulin, YML, and wild-type Fc are shown in magenta, cyan, brown, and green, respectively. The structures were superimposed based on the hFcRn α-chain and β2-microglobulin to highlight conformational shifts induced by YML mutations. b Molecular interactions within the hFcRn/YML and hFcRn/wild-type Fc complex models visualized using PyMOL. Notable interactions unique to YML include hydrophobic and electrostatic contacts between L428, R255, and Y436 of YML and residues of the hFcRn α-chain (P132, L135, N113, and E133). c Detailed molecular interactions depicted with LigPlot. Salt bridges and hydrogen bonds are indicated by red and green dotted lines, respectively. Additional interactions unique to YML, such as those involving Y309, M311, and R255, contribute to its enhanced binding kinetics under acidic conditions, compared to wild-type Fc