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PDBsum entry 1ff5
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Cell adhesion
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PDB id
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1ff5
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of e-Cadherin homoassociation.
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Authors
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O.Pertz,
D.Bozic,
A.W.Koch,
C.Fauser,
A.Brancaccio,
J.Engel.
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Ref.
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EMBO J, 1999,
18,
1738-1747.
[DOI no: ]
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PubMed id
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Abstract
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Electron microscopy of ECADCOMP, a recombinant E-cadherin ectodomain
pentamerized by the assembly domain of cartilage oligomeric matrix protein, has
been used to analyze the role of cis-dimerization and trans-interaction in the
homophilic association of this cell adhesion molecule. The Ca2+ dependency of
both interactions was investigated. Low Ca2+ concentrations (50 microM)
stabilized the rod-like structure of E-cadherin. At medium Ca2+ concentration
(500 microM), two adjacent ectodomains in a pentamer formed cis-dimers. At high
Ca2+ concentration (>1 mM), two cis-dimers from different pentamers formed a
trans-interaction. The X-ray structure of an N-terminal domain pair of
E-cadherin revealed two molecules per asymmetric unit in an intertwisted
X-shaped arrangement with closest contacts in the Ca2+-binding region between
domains 1 and 2. Contrary to previous data, Trp2 was docked in the hydrophobic
cavity of its own molecule, and was therefore not involved in cis-dimerization
of two molecules. This was supported further by W2A and A80I (a residue involved
in the hydrophobic cavity surrounding Trp2) mutations in ECADCOMP which both led
to abrogation of the trans- but not the cis-interaction. Structural and
biochemical data suggest a link between Ca2+ binding in the millimolar range and
Trp2 docking, both events being essential for the trans-association.
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Figure 4.
Figure 4 Final 2F[o]-F[c] stereoplot at a 1  contour
level of a region showing the hydrophobic cavity with (A) the
 A-strand
as in the M-ECAD12 structure and (B) the free tryptophan as in
the M-ECAD12+W structure. Continuous density (green) is observed
for the A-strand
(red), with chain tracing being unambiguous (A), whereas it
could only be traced from Ile4 in (B); additional density in the
hydrophobic pocket was interpreted as a free tryptophan. The
figure was prepared with DINO (Phillipsen, 1998).
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Figure 6.
Figure 6 Proposed scheme of the effect of calcium on
membrane-clustered E-cadherin. Low Ca^2+ concentrations
stabilize the rod-like structure (A and B), medium and high
concentrations result in cis-dimerization (C) and Trp2 docking
in its hydrophobic cavity which enables trans-interaction (D).
Domains 1–5 are drawn as gray blocks, with the hydrophobic
cavity to which Trp2 binds in domain 1. Trp2 is shown as a green
symbol with the A-strand
as a connecting black line. Bound Ca^2+ ions are symbolized by
circles and the different K[d] values of the distinct binding
sites by different colors: blue, 30  M;
red, 330 M;
yellow, 2 mM.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(1999,
18,
1738-1747)
copyright 1999.
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