|
Figure 4.
Figure 4: Argos, EGFR and structural homologues entrap the EGF
domain with two binding sites. a, The leftmost and rightmost
panels show EGF domains bound to Argos and the human EGFR
extracellular region^17 (sEGFR), respectively. Spitz is green
and hEGF is cyan. In the central upper panels, Spitz[EGF] and
hEGF are shown (in identical orientations) bound to Argos domain
2 (grey) and sEGFR domain I (beige). The side chains of
EGF-domain-interacting residues are drawn. Site 1 on sEGFR
domain I (defined in ref. 17) and its counterpart on Argos
(which includes site d2A) are marked by blue and red ovals,
respectively. In the lower central panels, Spitz[EGF] and hEGF
(again in identical orientations) are shown bound to Argos
domain 3 and sEGFR domain III. Sites 2 and 3 in the sEGFR/hEGF
interface are marked with blue ovals. Argos site d3B mimics
sEGFR site 2, but Argos does not mimic sEGFR site 3. Instead,
Argos makes a unique set of interactions with Spitz[EGF] (site
d3A). A key aliphatic side chain critical for the binding of
hEGF to site 3 of EGFR (L47 in hEGF, I98 in Spitz) is disordered
and exposed in the Spitz[EGF]–Argos complex. b, Domain
organization of uPAR^9, ^19. The three domains in uPAR are
coloured with the order used for Argos in Fig. 1. Like Argos,
uPAR uses three copies of this domain type—although in a
different arrangement—to form a C-clamp-like structure for
enveloping an EGF domain^9, ^19.
|
