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PDBsum entry 1o6s
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Bacterial infection
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PDB id
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1o6s
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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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Structure of internalin, A major invasion protein of listeria monocytogenes, In complex with its human receptor e-Cadherin.
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Authors
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W.D.Schubert,
C.Urbanke,
T.Ziehm,
V.Beier,
M.P.Machner,
E.Domann,
J.Wehland,
T.Chakraborty,
D.W.Heinz.
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Ref.
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Cell, 2002,
111,
825-836.
[DOI no: ]
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PubMed id
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Abstract
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Listeria monocytogenes, a food-borne bacterial pathogen, enters mammalian cells
by inducing its own phagocytosis. The listerial protein internalin (InlA)
mediates bacterial adhesion and invasion of epithelial cells in the human
intestine through specific interaction with its host cell receptor E-cadherin.
We present the crystal structures of the functional domain of InlA alone and in
a complex with the extracellular, N-terminal domain of human E-cadherin (hEC1).
The leucine rich repeat (LRR) domain of InlA surrounds and specifically
recognizes hEC1. Individual interactions were probed by mutagenesis and
analytical ultracentrifugation. These include Pro16 of hEC1, a major determinant
for human susceptibility to L. monocytogenes infection that is essential for
intermolecular recognition. Our studies reveal the structural basis for host
tro-pism of this bacterium and the molecular deception L. monocytogenes employs
to exploit the E-cadherin system.
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Figure 3.
Figure 3. The N-Terminal Domain of E-CadherinSuperposition
with related murine domains: Green – hEC1 (this paper); light
blue – murine E-cadherin (Pertz et al., 1999); blue – murine
N-cadherin (Tamura et al., 1998). β strand a′ is more closely
associated with strand b in hEC1 and is important for
intermolecular contacts between hEC1 and InlA′.
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Figure 4.
Figure 4. Detailed View of the Interactions between InlA′
and hEC1(A) All residue side chains involved in direct
interactions or as ligands to bridging ions/water are indicated
in ball-and-stick representation. Residues mutated in this study
are underlined. For InlA′ β strands (1–15 and a of Ig-like
domain) and adjacent coils are shown in violet. hEC1 is
represented by a continuous coil, β strands are indicated by
dark-green shading (labels a–g, connecting loops are indicated
by two letters to indicate flanking β strands). Cyan-, yellow-
and orange-colored spheres represent water, Ca^2+, and Cl^−,
respectively.(B) View of the hydrophobic pocket in InlA′,
which accommodates Pro16 of hEC1. In addition, the neighboring
residues Phe17 (side chain omitted) and Pro18 are involved in
specific interactions with InlA′. Hydrogen bonds are indicated
by green dotted lines. In murine, E-cadherin Pro16 is replaced
by glutamate (yellow model).(C) The octahedrally coordinated
Ca^2+ bridging InlA′and hEC1. The refined 2F[O]-F[C] map
contoured at 1σ is shown as a translucent surface.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2002,
111,
825-836)
copyright 2002.
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