Feature, Structure and Classifi cation of Adhesion Molecules: An Overview - Adhesion Molecules - page 5

(Aricescu and Jones 2007), with functional receptor-ligand interactions resulting
from the cumulative ef ect of many specii c, weak binding events. h ese clusters
require interactions outside of the primary ligand binding site in both cis (between
molecules on the same cell) and trans (between molecules on another cell surface)
as shown in Fig. 2 (Aricescu and Jones 2007). IgSF proteins form trans interactions
with molecules such as integrins ( Fig. 2 ). For example, the interaction between
intercellular adhesion molecule (ICAM-1) and specii c integrins probably involves
a heterophilic adhesion 'zipper' (Luo et al. 2007). Other IgSF proteins engage in
homophilic binding events and a double zipper-like adhesion complex appears to
stabilize NCAM adhesion.
INTEGRINS
h e integrins are a large family of CAMs involved in cell-cell adhesion and cell
interactions with the ECM proteins laminin, collagen, i bronectin and vitronectin.
h e extracellular domains of integrins bind to ECM proteins, while their cytoplasmic
domains engage the cell's cytoskeleton. Integrins mediate communication between
the extra- and intracellular environments; integrin-cytoskeleton interactions
af ect the binding ai nity and avidity of integrins for ECM ligands (inside-out
signaling), whereas ECM-integrin interactions lead to changes in the shape and
composition of the cell architecture (outside-in signaling) (Shimaoka et al. 2002).
All integrin-ligand interactions depend on the presence of divalent cations such as
Ca 2+ , Mg 2+ and Mn 2+ .
Integrin Structure: The a and b Subunits
Integrins are heterodimeric transmembrane glycoproteins, consisting of non-
covalently bound α and β subunits. Eighteen α and eight β subunits are described
in humans, assembling into 24 dif erent integrins (Arnaout et al. 2007). h e α
and β chains share no homology, being distinct polypeptides with specii c domain
structures. h e extracellular domains from both subunits contribute to the ligand-
binding site of the heterodimer (Takada et al. 2007).
h e extracellular domain of the α subunit contains seven repeats of
approximately 60 residues, which fold into a seven-bladed propeller structure
with β-sheets arranged around a central axis. A subset of integrin α chains have
an insertion domain (αA) containing a cation binding site, located between
repeats two and three of the propeller. C-terminal to the propeller is an Ig-like
h igh domain, followed by two β-sandwich modules, Calf-1 and Calf-2, and a
small transmembrane domain ( Fig. 3A ) (Humphries et al. 2003, Arnaout et al.
2007). h e intracellular domains of the α subunits show little homology, except for
a conserved motif proximal to the transmembrane region that associates with the
cytoplasmic tail of the β chain (Arnaout et al. 2007).