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PDBsum entry 1z9m
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Cell adhesion
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PDB id
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1z9m
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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 V domain of human nectin-Like molecule-1/syncam3/tsll1/igsf4b, A neural tissue-Specific immunoglobulin-Like cell-Cell adhesion molecule.
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Authors
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X.Dong,
F.Xu,
Y.Gong,
J.Gao,
P.Lin,
T.Chen,
Y.Peng,
B.Qiang,
J.Yuan,
X.Peng,
Z.Rao.
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Ref.
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J Biol Chem, 2006,
281,
10610-10617.
[DOI no: ]
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PubMed id
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Abstract
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Nectins are Ca(2+)-independent immunoglobulin (Ig) superfamily proteins that
participate in the organization of epithelial and endothelial junctions. Nectins
have three Ig-like domains in the extracellular region, and the first one is
essential in cell-cell adhesion and plays a central role in the interaction with
the envelope glycoprotein D of several viruses. Five Nectin-like molecules
(Necl-1 through -5) with similar domain structures to those of Nectins have been
identified. Necl-1 is specifically expressed in neural tissue, has
Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity, and
plays an important role in the formation of synapses, axon bundles, and
myelinated axons. Here we report the first crystal structure of its N-terminal
Ig-like V domain at 2.4 A, providing insight into trans-cellular recognition
mediated by Necl-1. The protein crystallized as a dimer, and the dimeric form
was confirmed by size-exclusion chromatography and chemical cross-linking
experiments, indicating this V domain is sufficient for homophilic interaction.
Mutagenesis work demonstrated that Phe(82) is a key residue for the adhesion
activity of Necl-1. A model for homophilic adhesion of Necl-1 at synapses is
proposed based on its structure and previous studies.
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Figure 4.
FIGURE 4. A, surface representation of the Necl-1 V domain
monomer. Hydrophobic residues are shown in white, acidic
residues in red, and basic residues in blue. Hydrophobic
interactions should be the main force in dimerization. B, the
homophilic binding interface of Necl-1 V domain. One Necl-1 V
monomer is shown in surface representation, and the other is
shown as a pink ribbon. The interface is formed mainly by
C-C'-C''-D  -strands and intervening
loops.
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Figure 8.
FIGURE 8. Schematic representation of the proposed
mechanism of homophilic adhesion mediated by Necl-1 at synapses,
based on the crystal structure. The cell surfaces are shown in
green with Necl-1 protruding from them. The Necl-1 monomers,
shown on the left, first form cis-dimers, and then form
trans-dimers, eventually causing cell-cell adhesion (shown on
the right).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
10610-10617)
copyright 2006.
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