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Crystal structure of Mip, a prolylisomerase from Legionella pneumophila

Nature Structural Biology volume 8, pages 779–783 (2001)Cite this article

Abstract

The human pathogen Legionella pneumophila, the etiological agent of the severe and often fatal Legionnaires' disease, produces a major virulence factor, termed 'macrophage infectivity potentiator protein' (Mip), that is necessary for optimal multiplication of the bacteria within human alveolar macrophages. Mip exhibits a peptidyl prolyl cis-trans isomerase (PPIase) activity, which appears to be important for infection. Here we report the 2.4 Å crystal structure of the Mip protein from L. pneumophila Philadelphia 1 and the 3.2 Å crystal structure of its complex with the drug FK506. Each monomer of the homodimeric protein consists of an N-terminal dimerization module, a long (65 Å) connecting α-helix and a C-terminal PPIase domain exhibiting similarity to human FK506-binding protein. In view of the recent significant increase in the number of reported cases of Legionnaires' disease and other intracellular infections, these structural results are of prime interest for the design of new drugs directed against Mip proteins of intracellular pathogens.

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Figure 1: Stereo view of a representative part of the electron density map.
Figure 2: Structure of LpMip.
Figure 3: Zinc ions as mediators of a crystal contact.
Figure 4: FK506 bound to the active site of LpMip.

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Acknowledgements

We thank A. Savoia and the staff of XRD beamline 5.2 at Elettra (Sincrotrone Trieste), Trieste, Italy, for help with data collection. FK506 was a gift from Fujisawa Pharmaceutical Co. This work was supported in part by the Deutsche Forschungsgemeinschaft. R.H., G.F. and J.H. thank the Fonds der Chemischen Industrie. This work is dedicated to the memory of L. Fonda and P.M. Fasella.

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  1. Alan Riboldi-Tunnicliffe

    Present address: Department of Chemistry, University of Glasgow, Joseph Black Building, Glasgow, G12 8QQ, UK

Authors and Affiliations

  1. Institute of Molecular Biotechnology, Beutenbergstr. 11, Jena, D-07745, Germany

    Alan Riboldi-Tunnicliffe, Sven Jessen, Manfred S. Weiss & Rolf Hilgenfeld

  2. Max Planck Research Unit 'Enzymology of Protein Folding', Weinbergweg 22, Halle, D-06120, Germany

    Bettina König, Jens Rahfeld & Gunter Fischer

  3. Institute for Molecular Biology of Infectious Diseases, University of Würzburg, Röntgenring 11, Würzburg, D-97070, Germany

    Jörg Hacker

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Correspondence to Rolf Hilgenfeld.

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Riboldi-Tunnicliffe, A., König, B., Jessen, S. et al. Crystal structure of Mip, a prolylisomerase from Legionella pneumophila. Nat Struct Mol Biol 8, 779–783 (2001). https://doi.org/10.1038/nsb0901-779

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