Biology Reference
In-Depth Information
canyon but rather attach to the most exposed star-shaped dome that
is encircled by the canyon. Three-dimensional structures of the rhi-
novirus serotypes HRV1A, HRV2, HRV3, HRV14, and HRV16 are
available at atomic resolution,
27,39-42
but the principles of receptor dis-
crimination could not be elucidated from these data.
The Receptors
ICAM-1 and LDL-receptors, both glycosylated type I transmem-
brane proteins, are completely different from each other in terms of
both function and structure (Fig. 1). ICAM-1 is predominantly
involved in cell-cell adhesion and in immune reactions by binding to
the integrins lymphocyte function associated antigen 1 (LFA1) and
macrophage differentiation antigen (Mac-1). Its extracellular part has
a rod-like structure of about 190 Å in length
45
and is composed of five
typical immunoglobulin-like domains of some 60 amino acid residues
each.
46
It possesses a short cytoplasmic tail of 29 residues without
typical clathrin-coated pit localization signals. An X-ray structure of
the two N-terminal domains at 2.2 Å is available.
47
Each domain is
roughly 35 Å long and has a diameter of about 20 Å.
43
Conversely,
members of the LDLR family function in ligand internalization and
signal transduction. Their ligand-binding domains are composed of
different numbers of ligand-binding repeats, or modules, containing
about 40 amino acid residues each. LDLR has seven such repeats,
while VLDLR has eight and LRP has 31. In LRP these are arranged
in clusters of 2, 8, 10, and 11 modules, counting from the N-terminus.
The repeats exhibit an ellipsoidal shape with axes of approximately
23 Å and 20 Å in length.
48
In LDLR and VLDLR, the ligand-binding
domain is followed by three regions with similarity to the epidermal
growth factor precursor (EGF-domain) that contain YWTD motives
forming a six-bladed
-propeller, a domain with O-glycosylation
proximal to the membrane, a transmembrane domain, and a cytoplas-
mic tail with an NPXY internalization motive.
49,50
The other mem-
bers of the LDLR family exhibit similar domain arrangements; LRP
might be considered a mosaic of several LDLR fragments with inter-
spaced EGF-domains and a longer cytoplasmic extension with several
internalization motives.
51
β
