Conformational epitope mapping by LFPD.
LFPD structure (a). The extracellular domain of rat and human HER2 was divided into 11 fragments (respectively of 106 and 109 amino acids): 6 contiguous core fragments plus 5 fragments overlapping the previous ones. Homology modeling of conformational epitopes (b). Molecular modeling analysis showed that the folding of each single fragment resembles the folding of the respective fragment in the entire molecule (blue zones). Only structures of hum1-2-4-5 fragments are shown for simplicity. Epitope mapping with Pertuzumab (c). Pertuzumab recognized only hum8 fragment on LFPD. Schematic representation of crystal structure of Pertuzumab (green)/hum8 fragment (red) complex (c, below). Epitope mapping with Trastuzumab (d). Trastuzumab recognized only hum11 fragment on LFPD (d). Schematic representation of cristal structure of Trastuzumab (green)/hum11 fragment (red) complex (d, below). Whole ECD of human HER2 was used as positive control (C+) (c, d).