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PDBsum entry 2wjs
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Cell adhesion
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PDB id
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2wjs
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the lg1-3 region of the laminin {alpha}2 chain.
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Authors
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F.Carafoli,
N.J.Clout,
E.Hohenester.
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Ref.
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J Biol Chem, 2009,
284,
22786-22792.
[DOI no: ]
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PubMed id
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Abstract
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Laminins are large heterotrimeric glycoproteins with many essential functions in
basement membrane assembly and function. Cell adhesion to laminins is mediated
by a tandem of five laminin G-like (LG) domains at the C terminus of the alpha
chain. Integrin binding requires an intact LG1-3 region, as well as
contributions from the coiled coil formed by the alpha, beta, and gamma chains.
We have determined the crystal structure at 2.8-A resolution of the LG1-3 region
of the laminin alpha2 chain (alpha2LG1-3). The three LG domains adopt typical
beta-sandwich folds, with canonical calcium binding sites in LG1 and LG2. LG2
and LG3 interact through a substantial interface, but LG1 is completely
dissociated from the LG2-3 pair. We suggest that the missing gamma chain tail
may be required to stabilize the interaction between LG1 and LG2-3 in the
biologically active conformation. A global analysis of N-linked glycosylation
sites shows that the beta-sandwich faces of LG1 are free of carbohydrate
modifications in all five laminin alpha chains, suggesting that these surfaces
may harbor the integrin binding site. The alpha2LG1-3 structure provides the
first atomic view of the integrin binding region of laminins.
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Figure 1.
Crystal structure of laminin α2LG1-3.A, schematic
representation of the structure. LG1, LG2, and LG3 are in green,
blue, and brown, respectively. Disulfide bridges are in yellow,
N-linked carbohydrate moieties are in magenta, and calcium ions
are shown as sky blue spheres. Disordered regions of the
polypeptide chain are indicated by dotted lines. The location of
the RRKRR motif in LG3 (see text) is indicated. B, stereoview of
a superposition of Cα traces of LG1 (green), LG2 (blue), and
LG3 (brown). Disulfide bridges are shown as thick sticks. The 14
canonical β-strands of laminin LG domains (31) have been
labeled sequentially, A–N.
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Figure 4.
Location of N-linked glycosylation sites in the LG1-3
structure. Shown are two surface representations of the α2LG1-3
structure (LG1, green; LG2, blue; LG3, brown) related by a
rotation of 180° about a vertical axis. The LG1-2 linker is
shown as a black line. The predicted attachment site in LG1 of
the coiled coil region is indicated by a gray arrow. Every
N-linked glycosylation site present in one or more of the five
mouse or human laminin α chains has been mapped onto the
α2LG1-3 structure (see text) and marked by a branched core
hexasaccharide (magenta). The left view is similar to the one in
Fig. 1A.
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The above figures are
reprinted
from an Open Access publication published by the ASBMB:
J Biol Chem
(2009,
284,
22786-22792)
copyright 2009.
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