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Structure of the cell-adhesion fragment of intimin from enteropathogenic Escherichia coli

Nature Structural Biology volume 6, pages 313–318 (1999)Cite this article

Abstract

Enteropathogenic Escherichia coli (EPEC) induce gross cytoskeletal rearrangement within epithelial cells, immediately beneath the attached bacterium. The C-terminal 280 amino acid residues of intimin (Int280; 30.1 kDa), a bacterial cell-adhesion molecule, mediate the intimate bacterial host–cell interaction. Recently, interest in this process has been stimulated by the discovery that the bacterial intimin receptor protein (Tir) is translocated into the host cell membrane, phosphorylated, and after binding intimin triggers the intimate attachment. Using multidimensional nuclear magnetic resonance (NMR) and combining perdeuteration with site-specific protonation of methyl groups, we have determined the global fold of Int280. This represents one of the largest, non-oligomeric protein structures to be determined by NMR that has not been previously resolved by X-ray crystallography. Int280 comprises three domains; two immunoglobulin-like domains and a C-type lectin-like module, which define a new family of bacterial adhesion molecules. These findings also imply that carbohydrate recognition may be important in intimin-mediated cell adhesion.

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Figure 3: Topology and sequence alignment for Int280.
Figure 2: Structure of Int280.
Figure 4: Schematic representations of the structural comparison between Int280 domains with other known structures.
Figure 1: Summary of NOE data.

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Acknowledgements

SM is indebted for the financial support of The Wellcome Trust and the BBSRC. G.D. and G.F. would also like to acknowledge the support of The Wellcome Trust.

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Authors and Affiliations

  1. Department of Biochemistry Imperial College of Science, Technology and Medicine, Exhibition Road, South Kensington, SW7 2AY, London, UK

    Geoff Kelly, Sunil Prasannan, Keiran Fleming, Gad Frankel, Gordon Dougan & Stephen Matthews

  2. Centre for Structural Biology, Imperial College of Science, Technology and Medicine, Exhibition Road, South Kensington, SW7 2AY, London, UK

    Geoff Kelly, Sunil Prasannan, Keiran Fleming & Stephen Matthews

  3. Institute of Food Research, Reading Laboratory, Earley Gate, Whiteknights Road, RG6 6BZ, Reading, UK

    Sarah Daniell & Ian Connerton

  4. Wellcome Centre for Infectious Diseases, Imperial College of Science, Technology and Medicine, Exhibition Road, South Kensington, SW7 2AY, London, UK

    Gad Frankel & Gordon Dougan

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Correspondence to Stephen Matthews.

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Kelly, G., Prasannan, S., Daniell, S. et al. Structure of the cell-adhesion fragment of intimin from enteropathogenic Escherichia coli. Nat Struct Mol Biol 6, 313–318 (1999). https://doi.org/10.1038/7545

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