PDBsum entry 1f02

Cell adhesion

PDB id: 1f02

Contents

Protein chains

282 a.a. *

66 a.a. *

* Residue conservation analysis

PDB id:

1f02

Name:

Cell adhesion

Title:

Crystal structure of c-terminal 282-residue fragment of intimin in complex with translocated intimin receptor (tir) intimin-binding domain

Structure:

Intimin. Chain: i. Fragment: c-terminal domain (282 residues). Engineered: yes. Translocated intimin receptor. Chain: t. Fragment: intimin-binding domain. Synonym: tir. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Tetramer (from PDB file)

Resolution:

2.90Å R-factor: 0.247 R-free: 0.296

Authors:

Y.Luo,E.A.Frey,R.A.Pfuetzner,A.L.Creagh,D.G.Knoechel,C.A.Haynes, B.B.Finlay,N.C.J.Strynadka

Key ref:

Y.Luo et al. (2000). Crystal structure of enteropathogenic Escherichia coli intimin-receptor complex. Nature, 405, 1073-1077. PubMed id: 10890451 DOI: 10.1038/35016618

Date:

14-May-00 Release date: 12-Jul-00

Protein chain

P19809  (EAE_ECO27) -  Intimin from Escherichia coli O127:H6 (strain E2348/69 / EPEC)

Seq: 939 a.a.

Struc: 282 a.a.

Protein chain

Q9KWH9  (Q9KWH9_ECOLX) -  Translocated intimin receptor Tir from Escherichia coli

Seq: 552 a.a.

Struc: 66 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/35016618

Nature 405:1073-1077 (2000)

PubMed id: 10890451

Crystal structure of enteropathogenic Escherichia coli intimin-receptor complex.

Y.Luo, E.A.Frey, R.A.Pfuetzner, A.L.Creagh, D.G.Knoechel, C.A.Haynes, B.B.Finlay, N.C.Strynadka.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2000, 405, 1073-1077) copyright 2000.

Figures were selected by an automated process.