The Epidermal Growth Factor (EGF) receptor is a
tyrosine kinase that mediates the biological effects of
ligands such as EGF and transforming growth factor alpha.
An understanding of the molecular basis of its action has
been hindered by a lack of structural and mutational data
on the receptor. We have constructed comparative models
of the four extracellular domains of the EGF receptor that
are based on the structure of the first three domains of
the insulin-like growth factor-1 (IGF-1) receptor. The
first and third domains of the EGF receptor, L1 and L2,
are right-handed beta helices. The second and fourth domains
of the EGF receptor, S1 and S2, consist of the modules
held together by disulfide bonds, which, except for the
first module of the S1 domain, form rod-like structures.
The arrangement of the L1 and S1 domains of the model are
similar to that of the first two domains of the IGF-1 receptor,
whereas that of the L2 and S2 domains appear to be significantly
different. Using the EGF receptor model and limited information
from the literature, we have proposed a number of regions
that may be involved in the functioning of the receptor.
In particular, the faces containing the large beta sheets
in the L1 and L2 domains have been suggested to be involved
with ligand binding of EGF to its receptor.