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PDBsum entry 1f02
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Cell adhesion
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PDB id
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1f02
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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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Crystal structure of enteropathogenic escherichia coli intimin-Receptor complex.
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Authors
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Y.Luo,
E.A.Frey,
R.A.Pfuetzner,
A.L.Creagh,
D.G.Knoechel,
C.A.Haynes,
B.B.Finlay,
N.C.Strynadka.
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Ref.
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Nature, 2000,
405,
1073-1077.
[DOI no: ]
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PubMed id
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Abstract
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Intimin and its translocated intimin receptor (Tir) are bacterial proteins that
mediate adhesion between mammalian cells and attaching and effacing (A/E)
pathogens. Enteropathogenic Escherichia coli (EPEC) causes significant
paediatric morbidity and mortality world-wide. A related A/E pathogen,
enterohaemorrhagic E. coli (EHEC; O157:H7) is one of the most important
food-borne pathogens in North America, Europe and Japan. A unique and essential
feature of A/E bacterial pathogens is the formation of actin-rich pedestals
beneath the intimately adherent bacteria and localized destruction of the
intestinal brush border. The bacterial outer membrane adhesin, intimin, is
necessary for the production of the A/E lesion and diarrhoea. The A/E bacteria
translocate their own receptor for intimin, Tir, into the membrane of mammalian
cells using the type III secretion system. The translocated Tir triggers
additional host signalling events and actin nucleation, which are essential for
lesion formation. Here we describe the the crystal structures of an EPEC intimin
carboxy-terminal fragment alone and in complex with the EPEC Tir intimin-binding
domain, giving insight into the molecular mechanisms of adhesion of A/E
pathogens.
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Figure 1.
Figure 1: The EPEC/host-cell adhesion interface. The model is
based on our structural data of the complex of the C-terminal
fragment of intimin (domains D1, D2 and D3) and the
extracellular Tir IBD. Intimin is shown in green with domains
labelled and boundary residues numbered. The Ig-like domains D0,
D1 and D2 are shown as rectangles, and the lectin-like domain
D3, which binds to the Tir IBD, as an oval. Tir is shown as a
dimer (in pink and dark blue) in the host-cell membrane, and is
also labelled and numbered as described for intimin. The Tir IBD
is the extracellular component of Tir flanked by the two
predicted transmembrane (TM) domains. We observe a dimeric Tir
IBD, with the two helices in each monomer forming a four-helix
bundle that is stabilized by multiple hydrophobic and
hydrogen-bonded interactions. The N-terminal domain of Tir
anchors host cytoskeletal components (such as actin) that are
needed to form the characteristic A/E lesion on the host-cell
surface upon bacterial adhesion.
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Figure 3.
Figure 3: GRASP11 surface representation of the dimeric
intimin-Tir IBD complex. The viewing direction is
approximately parallel to the dimerization dyad. Accessible
surfaces colour-coded with electrostatic potential (-15 for red,
+10 for blue) are shown for one intimin (on the left) and one
Tir IBD (in the centre). The other intimin (in blue) and Tir IBD
(in pink) are shown as worm models. Although Tir IBD has an
overall net negative charge (seven net negative charges) the
dimerization interface between the two Tir molecules is
minimally charged. Intimin has a complementary overall positive
charge (six net positive charges) with a positively charged tip
close to the  -helices
of the Tir IBD dimer.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2000,
405,
1073-1077)
copyright 2000.
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