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Crystal structure of enteropathogenic Escherichia coli intimin–receptor complex

Nature volume 405, pages 1073–1077 (2000)Cite this article

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-wide1. 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 border2. The bacterial outer membrane adhesin, intimin3, is necessary for the production of the A/E lesion and diarrhoea4. The A/E bacteria translocate their own receptor for intimin, Tir5, 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: The EPEC/host-cell adhesion interface.
Figure 2: A RIBBONS30 representation of the intimin and Tir IBD dimer complex.
Figure 3: GRASP11 surface representation of the dimeric intimin–Tir IBD complex.
Figure 4: Stereo RIBBONS30 representation of intimin D3 (colour-coded by secondary structures) and Tir IBD (in pink) with side chains of the residues involved in intimin–Tir recognition.

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Acknowledgements

We thank S. Mosimann for suggestions on the Se-Met intimin derivative, F. Ness for help in the production of Fig. 1, and D. Lim and S. Mosimann for software support. Work in our laboratories was supported by the Medical Research Council (MRC) of Canada, the Canadian Bacterial Disease Network Center of Excellence, Burroughs Wellcome Foundation (BWF) and the Toronto Hospital for Sick Children. N.C.J.S. is an MRC Scholar and a BWF New Investigator, and B.B.F. is an MRC Scientist and a Howard Hughes International Research Scholar.

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  1. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, V6T 1Z3, British Columbia , Canada

    Yu Luo, Elizabeth A. Frey, Richard A. Pfuetzner, Derek G. Knoechel, B. Brett Finlay & Natalie C. J. Strynadka

  2. Biotechnology Laboratory, University of British Columbia, Vancouver, V6T 1Z3, British Columbia , Canada

    Yu Luo, Elizabeth A. Frey, Richard A. Pfuetzner, A. Louise Creagh, Derek G. Knoechel, Charles A. Haynes, B. Brett Finlay & Natalie C. J. Strynadka

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Luo, Y., Frey, E., Pfuetzner, R. et al. Crystal structure of enteropathogenic Escherichia coli intimin–receptor complex. Nature 405, 1073–1077 (2000). https://doi.org/10.1038/35016618

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