BINDING OF THE ALPHA(2) INTEGRIN-I DOMAIN TO EXTRACELLULAR-MATRIX LIGANDS - STRUCTURAL AND MECHANISTIC DIFFERENCES BETWEEN COLLAGEN AND LAMININ-BINDING
Sk. Dickeson et al., BINDING OF THE ALPHA(2) INTEGRIN-I DOMAIN TO EXTRACELLULAR-MATRIX LIGANDS - STRUCTURAL AND MECHANISTIC DIFFERENCES BETWEEN COLLAGEN AND LAMININ-BINDING, Cell adhesion and communication (Softback), 5(4), 1998, pp. 273-281
The alpha(2)beta(1) integrin functions as a cell surface receptor for
collagen on some cells and as both a collagen and laminin receptor on
a more restricted subset of cell types including endothelial and epith
elial cells. The alpha(2) integrin subunit I domain binds collagen in
a divalent cation-dependent manner. In contrast, I domain binding to l
aminin occurs via both divalent cation-dependent and -independent mech
anisms. Saturable binding was observed in the presence of either Mn2or EDTA, although the extent of binding in Mn2+ was twice that observe
d in EDTA. Half-maximal binding occurred at about 22 nM I domain in ei
ther case. Whereas laminin binding was significantly enhanced by Mn2+,
with half-maximal binding occurring at 1.9 mM Mn2+ Mg2+ was much less
effective. Deletion of the N-terminal 35 residues of the I domain, in
cluding the DXSXS portion of the MIDAS motif, caused a significant dim
inution of laminin binding activity. Laminin binding by the I domain w
as significantly inhibited by the alpha(2)beta(1) function-blocking an
tibody 6F1 in the presence of either EDTA or Mn2+. The non-function-bl
ocking antibody 12F1 had no effect. In contrast to the binding of the
alpha(2) integrin I domain to collagen, the laminin binding activity o
f the I domain was not enhanced by the addition of the first EF hand m
otif of the integrin.