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Lactococcal bacteriophage p2 receptor-binding protein structure suggests a common ancestor gene with bacterial and mammalian viruses

Nature Structural & Molecular Biology volume 13, pages 8589 (2006) | Download Citation

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Abstract

Lactococcus lactis is a Gram-positive bacterium used extensively by the dairy industry for the manufacture of fermented milk products. The double-stranded DNA bacteriophage p2 infects specific L. lactis strains using a receptor-binding protein (RBP) located at the tip of its noncontractile tail. We have solved the crystal structure of phage p2 RBP, a homotrimeric protein composed of three domains: the shoulders, a β-sandwich attached to the phage; the neck, an interlaced β-prism; and the receptor-recognition head, a seven-stranded β-barrel. We used the complex of RBP with a neutralizing llama VHH domain to identify the receptor-binding site. Structural similarity between the recognition-head domain of phage p2 and those of adenoviruses and reoviruses, which invade mammalian cells, suggests that these viruses, despite evolutionary distant targets, lack of sequence similarity and the different chemical nature of their genomes (DNA versus RNA), might have a common ancestral gene.

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Acknowledgements

This work was supported by the Marseille-Nice Genopole, by the European Union's Structural Proteomics in Europe program (fifth PCRDT, QLG2-CT-2002-00988) and by a grant from the Natural Sciences and Engineering Research Council of Canada. C. Huyghe is greatly acknowledged for protein production and D. Tremblay (Laval University, Quebec, Canada) for phage p2 DNA.

Author information

Affiliations

  1. Architecture et Fonction des Macromolécules Biologiques, UMR 6098 CNRS and Universités d'Aix-Marseille I & II, Campus de Luminy, 163 Av. de Luminy 13288 Marseille Cedex 9, France.

    • Silvia Spinelli
    • , Aline Desmyter
    •  & Christian Cambillau
  2. Department of Biotechnology, Unilever Research Vlaardingen, Oliver van Noortlaan 120, 3133 AT Vlaardigen, The Netherlands.

    • C Theo Verrips
    •  & Hans J W de Haard
  3. Department of Molecular Cell Biology, EMSA, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands.

    • C Theo Verrips
  4. Ablynx, Technologiepark 4, 9052 Zwijnaarde, Belgium.

    • Hans J W de Haard
  5. Groupe de Recherche en Écologie Buccale and the Félix d'Hérelle Reference Center for Bacterial Viruses, Faculté de Médecine Dentaire and Département de Biochimie et de Microbiologie, Faculté des Sciences et de Génie, Université Laval, Québec City, Québec, Canada G1K 7P4.

    • Sylvain Moineau

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Christian Cambillau.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Top view of the p2 rbp head–VHH5 complex.

  2. 2.

    Supplementary Fig. 2

    Electron density map of residues 230–234.

  3. 3.

    Supplementary Table 1

    Interactions of the receptor binding domain with VHH mono5

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DOI

https://doi.org/10.1038/nsmb1029

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