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Figure 5.
Figure 5. Implications for the Mechanism of Inhibition of
EGFR by Matuzumab
(A) Cartoon of the extended sEGFR with
Fab72000, in surface representation, docked onto its domain III
epitope. The orientation of the receptor is the same as for the
right-hand protomer in the sEGFR dimer shown in Figure 1 (with
domains colored as for the left-hand protomer; EGF is omitted
for clarity). The Fab72000 is colored as in Figure 3. The
N-terminal region of domain I clashes with the V[L] domain
(indicated with an arrow). Additional clashes occur along the
C-terminal half of domain II (see [B]). The C-terminal loop on
domain II (D278, H280) that makes critical contacts across the
dimer interface is marked with an asterisk.
(B) In this
view, an approximate 50° rotation about the vertical axis
relative to (A), domain II is shown in sphere representation in
dark green. A cartoon of domain II of the other molecule in the
dimer is shown (light green) for reference. Domain I has been
omitted for clarity. The V[L] domain of the Fab clashes with
domain II in the critical C-terminal region that forms the
binding pocket for the dimerization arm and makes important
contacts with domain III (from N274 and E293 in domain II,
colored orange). These interactions are known to be crucial for
stabilizing the dimerization competent conformation of domain
II. The Fab72000 epitope loop on domain III is colored in red.
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