TY - JOUR
T1 - Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI
AU - Brondijk, T.H.C.
AU - de Ruiter, T.
AU - Ballering, J.
AU - Wienk, H.
AU - Lebbink, R.J.
AU - van Ingen, H.
AU - Boelens, R.
AU - Farndale, R.W.
AU - Meyaard, L.
AU - Huizinga, E.G.
PY - 2010
Y1 - 2010
N2 - Leukocyte-associated immunoglobulinlike
receptor-1 (LAIR-1), one of the most
widely spread immune receptors, attenuates
immune cell activation when bound
to specific sites in collagen. The collagenbinding
domain of LAIR-1 is homologous
to that of glycoprotein VI (GPVI), a collagen
receptor crucial for platelet activation.
Because LAIR-1 and GPVI also
display overlapping collagen-binding
specificities, a common structural basis
for collagen recognition would appear
likely. Therefore, it is crucial to gain insight
into the molecular interaction of
both receptors with their ligand to prevent
unwanted cross-reactions during
therapeutic intervention. We determined
the crystal structure of LAIR-1 and
mapped its collagen-binding site by
nuclear magnetic resonance (NMR) titrations
and mutagenesis. Our data identify
R59, E61, and W109 as key residues for
collagen interaction. These residues are
strictly conserved in LAIR-1 and GPVI
alike; however, they are located outside
the previously proposed GPVI collagenbinding
site. Our data provide evidence
for an unanticipated mechanism of collagen
recognition common to LAIR-1 and
GPVI. This fundamental insight will contribute
to the exploration of specific means
of intervention in collagen-induced signaling
in immunity and hemostasis. (Blood.
2010;115:1364-1373).
AB - Leukocyte-associated immunoglobulinlike
receptor-1 (LAIR-1), one of the most
widely spread immune receptors, attenuates
immune cell activation when bound
to specific sites in collagen. The collagenbinding
domain of LAIR-1 is homologous
to that of glycoprotein VI (GPVI), a collagen
receptor crucial for platelet activation.
Because LAIR-1 and GPVI also
display overlapping collagen-binding
specificities, a common structural basis
for collagen recognition would appear
likely. Therefore, it is crucial to gain insight
into the molecular interaction of
both receptors with their ligand to prevent
unwanted cross-reactions during
therapeutic intervention. We determined
the crystal structure of LAIR-1 and
mapped its collagen-binding site by
nuclear magnetic resonance (NMR) titrations
and mutagenesis. Our data identify
R59, E61, and W109 as key residues for
collagen interaction. These residues are
strictly conserved in LAIR-1 and GPVI
alike; however, they are located outside
the previously proposed GPVI collagenbinding
site. Our data provide evidence
for an unanticipated mechanism of collagen
recognition common to LAIR-1 and
GPVI. This fundamental insight will contribute
to the exploration of specific means
of intervention in collagen-induced signaling
in immunity and hemostasis. (Blood.
2010;115:1364-1373).
U2 - 10.1182/blood-2009-10-246322
DO - 10.1182/blood-2009-10-246322
M3 - Article
SN - 0006-4971
VL - 115
SP - 1364
EP - 1373
JO - Blood
JF - Blood
IS - 7
ER -