Fig. 2: Fc-MST-HN combines a larger hydrophobic-binding epitope on FcRn than on Fc-MST50 with the expected upside-down mode of interaction.
From: The Fab region of IgG impairs the internalization pathway of FcRn upon Fc engagement
A Superposition of the crystallographic models of complexes between FcRn:Ăź2M (green and orange) and Fc-MST (yellow) or Fc-MST-HN (red), displayed in cartoon representation. The linker region connecting the extracellular region of FcRn to its transmembrane domain is represented as a dashed line. If present, Fab moieties would be oriented downwards and sterically clash with the membrane, which is shown for clarity. Detailed view of superimposed residues that contribute (B) electrostatically and (C) hydrophobically to the Fc:FcRn interface. Main chains are shown as ribbons, indicated side chains are shown as sticks. D Top view of the superimposed models, showing that accommodation of F434 in Fc-MST-HN (red) instead of N434 in Fc-MST (yellow) only requires a local conformational change by FcRn (green) at positions 130 and 135. Main chains shown as ribbons, indicated side chains are shown as sticks. E Side view of the superimposed models, detailing how F434 (red, stick representation) of Fc-MST-HN (red, ribbon representation) makes use of a hydrophobic pocket adjacent to L135 and P132. FcRn is shown in surface representation.
