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PDBsum entry 2v37
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Cell adhesion
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PDB id
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2v37
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References listed in PDB file
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Key reference
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Title
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Insights into the low adhesive capacity of human t-Cadherin from the nmr structure of its n-Terminal extracellular domain.
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Authors
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S.A.Dames,
E.Bang,
D.Haüssinger,
T.Ahrens,
J.Engel,
S.Grzesiek.
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Ref.
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J Biol Chem, 2008,
283,
23485-23495.
[DOI no: ]
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PubMed id
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Abstract
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T-cadherin is unique among the family of type I cadherins, because it lacks
transmembrane and cytosolic domains, and attaches to the membrane via a
glycophosphoinositol anchor. The N-terminal cadherin repeat of T-cadherin
(Tcad1) is approximately 30% identical to E-, N-, and other classical cadherins.
However, it lacks many amino acids crucial for their adhesive function of
classical cadherins. Among others, Trp-2, which is the key residue forming the
canonical strand-exchange dimer, is replaced by an isoleucine. Here, we report
the NMR structure of the first cadherin repeat of T-cadherin (Tcad1). Tcad1, as
other cadherin domains, adopts a beta-barrel structure with a Greek key folding
topology. However, Tcad1 is monomeric in the absence and presence of calcium.
Accordingly, lle-2 binds into a hydrophobic pocket on the same protomer and
participates in an N-terminal beta-sheet. Specific amino acid replacements
compared to classical cadherins reduce the size of the binding pocket for
residue 2 and alter the backbone conformation and flexibility around residues 5
and 15 as well as many electrostatic interactions. These modifications
apparently stabilize the monomeric form and make it less susceptible to a
conformational switch upon calcium binding. The absence of a tendency for
homoassociation observed by NMR is consistent with electron microscopy and
solid-phase binding data of the full T-cadherin ectodomain (Tcad1-5). The
apparent low adhesiveness of T-cadherin suggests that it is likely to be
involved in reversible and dynamic cellular adhesion-deadhesion processes, which
are consistent with its role in cell growth and migration.
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Figure 2.
FIGURE 2. The NMR structure of Tcad1. Tcad1 adopts as the
other characterized cadherin domains a β-barrel structure (A)
with a Greek key folding topology (B). Open boxes mark residues
with a β-bulge conformation. As Tcad1 is monomeric in the
presence and absence of calcium, residues Ile-2-Val-3 and
Val-25-Asp-26 can participate in a stable β-sheet structure
(pink colored strands). The pairing of the strands is
antiparallel except for the parallel arrangement of strands B
and I. A stereoview of the superposition of the 20 final in a
water shell refined structures is shown in C. The β-strands are
colored as in A and B. Glycines with positive  -angles
are depicted in yellow and prolines that adopt a cis-peptide
bond conformation in red. All structure pictures were made with
the programs MolMol (49) and POV-Ray.
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Figure 4.
FIGURE 4. Calcium binding to Tcad1. For this
representation, the chemical shift changes in ^1H-^15N-HSQC of
Tcad1 with different concentrations of Ca^2+ (supplemental Fig.
S4) have been mapped onto a space-filling model of Tcad1 (middle
and right). Strong (red) and weak (orange) chemical shift
changes are observed only for residues in proximity to the
calcium binding sites (residues with green colored side chains
in the ribbon representation to the left, see also Fig. 1B).
Residues colored in yellow shift only very weakly.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2008,
283,
23485-23495)
copyright 2008.
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