Table 1.
The identity of human HER2 protein in the UniPort database.
Table 2.
The structurally conserved motifs of ECD HER2 detected by PROSITE Scan.
Figure 1.
The location of the three structurally conserved motifs (F1, F2 and F3) on ECD HER2 crystal structure.
Purple: ECD HER2 receptor; Yellow: structurally conserved motifs (F1, F2 and F3). N(C) and C(C) are ECD HER2's N-terminal and C-terminal, respectively.
Figure 2.
Comparison of structurally conserved motifs of ECD HER2 with the epitope of trastuzumab.
A: The location of F1, F2 and F3 in the tube worm representation of the HER2-trastuzumab complex. HER2 is colored dark brown and trastuzumab is in chain form: light chain in bright purple and heavy chain in blue. The structurally conserved motifs (F1, F2 and F3) are highlighted in yellow. B: Enlarged view of binding interface between ECD HER2 and trastuzumab. Trastuzumab is shown in grey, with a space-fill protein backbone and side chains style. The numbers indicted in the figure show the three loop regions (highlighted in yellow) mediating the interaction with trastuzumab. F2 is shown in light green and F3 is in bright purple. The overlapped residues between F2, F3 and interaction loops are P557 and E558 (F2, on loop 1 (P557-D561)), D570, P571, P572 and F573 (F3, on loop 2 (D570-F573)), K593, F594, P595, D596, E597 and E598 (F3, on loop 3 (K593-P603)). According to the crystal structure of HER2-trastuzumab complex [33], there are eight residues invisible in the F3 region. The numbers shown in the figure are consistent with PDB data rather than sequential numbering for HER2 residues.
Figure 3.
Comparison of structurally conserved motifs of ECD HER2 with the epitope of pertuzumab Fab.
A: The location of F1 in the tube worm representation of the HER2-pertuzumab complex. According to Franklin, M.C. et al. [14], ECD HER2 is colored according to domain: domain I in pink, domain II in blue, domain III in dark purple and domain IV in grey. Pertuzumab is shown as a chain: light chain in green and heavy chain in dark grey. The highlighted in yellow shows the location of structurally conserved F1. B: The enlarged view shows the binding interface between ECD HER2 and pertuzumab. Domain II is shown in blue, and the F1 is shown as a tube worm with wire side-chains in dark green. The residues involving in the interaction with pertuzumab [14] are highlighted in yellow. The numbers shown in the figure are consistent with PDB data rather than sequential numbering for HER2 residues.
Table 3.
The linearly conserved motifs (fingerprints) of ECD HER2 searched by PRINTS.