Fig. 1: Structural and sequence analysis of i-shaped antibodies (iAbs).
From: i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists
a Structural representation of the domain-exchanged iAb 2G12 (left, PDB: 2OQJ) and two representative iAbs from the DH851 and DH898 affinity interface lineages, DH851.3 (middle, PDB: 7LU9) and DH898.1 (right, PDB: 7L6M). The light chain (LC) and heavy chain (HC) from each Fab is labeled within each structure. Insets highlight the interface between the heavy chain variable (VH) domains of the two Fabs with residues involved shown as sticks. b Table of amino acid residues in the VH domain predicted to contribute to the iAb conformation. VH domain residues are shown using Kabat numbering. The sequence logos below the table are based on the distribution of amino acids at the indicated residue across all human antibody sequences within the abYsis database. Residues shown in red are rare mutations present in <1% of all deposited human sequences. Asterisks denote additional, non-native hydrophobic substitutions previously shown to strengthen the affinity interfaces from the DH851 and DH898 lineages. A representative example of iAb mutation grafting onto anti-OX40 antibodies is shown in Fig. S1.
