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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 85–89 (2006)Cite this article

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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Figure 1: The receptor-binding protein from lactococcal phage p2.
Figure 2: Individual domains of the receptor-binding protein from phage p2.
Figure 3: The complex of the phage p2 RBP head with VHH5.

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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

Authors and 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, Marseille, 13288 Cedex 9, France

    Silvia Spinelli, Aline Desmyter & Christian Cambillau

  2. Department of Biotechnology, Unilever Research Vlaardingen, Oliver van Noortlaan 120, Vlaardigen, 3133 AT, The Netherlands

    C Theo Verrips & Hans J W de Haard

  3. Department of Molecular Cell Biology, EMSA, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands

    C Theo Verrips

  4. Ablynx, Technologiepark 4, Zwijnaarde, 9052, Belgium

    Hans J W de Haard

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

    Sylvain Moineau

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  1. Silvia Spinelli
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Correspondence to Christian Cambillau.

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Supplementary information

Supplementary Fig. 1

Top view of the p2 rbp head–VHH5 complex. (PDF 990 kb)

Supplementary Fig. 2

Electron density map of residues 230–234. (PDF 806 kb)

Supplementary Table 1

Interactions of the receptor binding domain with VHH mono5 (PDF 53 kb)

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Spinelli, S., Desmyter, A., Verrips, C. et al. Lactococcal bacteriophage p2 receptor-binding protein structure suggests a common ancestor gene with bacterial and mammalian viruses. Nat Struct Mol Biol 13, 85–89 (2006). https://doi.org/10.1038/nsmb1029

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