The protein–protein interaction map of Helicobacter pylori

An Erratum to this article was published on 08 February 2001


With the availability of complete DNA sequences for many prokaryotic and eukaryotic genomes, and soon for the human genome itself, it is important to develop reliable proteome-wide approaches for a better understanding of protein function1. As elementary constituents of cellular protein complexes and pathways, protein–protein interactions are key determinants of protein function. Here we have built a large-scale protein–protein interaction map of the human gastric pathogen Helicobacter pylori. We have used a high-throughput strategy of the yeast two-hybrid assay to screen 261 H. pylori proteins against a highly complex library of genome-encoded polypeptides2. Over 1,200 interactions were identified between H. pylori proteins, connecting 46.6% of the proteome. The determination of a reliability score for every single protein–protein interaction and the identification of the actual interacting domains permitted the assignment of unannotated proteins to biological pathways.

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Figure 1: Outline of the strategy for building an H. pylori (Hp) proteome-wide interaction map.
Figure 2: Sets of E. coli interaction data for which H. pylori orthologous proteins were identified and assayed in interaction screens.
Figure 3: PIMRider screen shots.
Figure 4: Alignment between H. pylori HP1247 protein and E. coli HolA.


  1. 1

    Fields, S. The future is function. Nature Genet. 15, 325–327 (1997).

    CAS  Article  Google Scholar 

  2. 2

    Fromont-Racine, M., Rain, J. C. & Legrain, P. Toward a functional analysis of the yeast genome through exhaustive two-hybrid screens. Nature Genet. 16, 277–282 (1997).

    CAS  Article  Google Scholar 

  3. 3

    Bartel, P. L., Roecklein, J. A., SenGupta, D. & Fields, S. A protein linkage map of Escherichia coli bacteriophage T7. Nature Genet. 12, 72–77 (1996).

    CAS  Article  Google Scholar 

  4. 4

    Flajolet, M. et al. A genomic approach of the hepatitis C virus generates a protein interaction map. Gene 242, 369– 379 (2000).

    CAS  Article  Google Scholar 

  5. 5

    McCraith, S., Holtzman, T., Moss, B. & Fields, S. Genome-wide analysis of vaccinia virus protein–protein interactions. Proc. Natl Acad. Sci. USA 97, 4879–4884 (2000).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Ito, T. et al. Toward a protein–protein interaction map of the budding yeast: A comprehensive system to examine two-hybrid interactions in all possible combinations between the yeast proteins. Proc. Natl Acad. Sci. USA 97, 1143–1147 ( 2000).

    ADS  CAS  Article  Google Scholar 

  7. 7

    Uetz, P. et al. A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae. Nature 403, 623–627 (2000).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Walhout, A. J. M. et al. Protein interaction mapping in C. elegans using proteins involved in vulval development. Science 287, 116–122 (2000).

    ADS  CAS  Article  Google Scholar 

  9. 9

    Tomb, J. F. et al. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388, 539– 547 (1997).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Bairoch, A. & Apweiler, R. The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000. Nucleic Acids Res. 28, 45–48 ( 2000).

    CAS  Article  Google Scholar 

  11. 11

    Alm, R. A. et al. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397, 176–180 (1999).

    ADS  Article  Google Scholar 

  12. 12

    Moszer, I. The complete genome of Bacillus subtilis: from sequence annotation to data management and analysis. FEBS Lett. 430, 28–36 (1998).

    CAS  Article  Google Scholar 

  13. 13

    Welch, M., Chinardet, N., Mourey, L., Birck, C. & Samama, J. P. Structure of the CheY-binding domain of histidine kinase CheA in complex with CheY. Nature Struct. Biol. 5, 25–29 ( 1998).

    CAS  Article  Google Scholar 

  14. 14

    Cussac, V., Ferrero, R. L. & Labigne, A. Expression of Helicobacter pylori urease genes in Escherichia coli grown under nitrogen-limiting conditions. J. Bacteriol. 174, 2466–2473 (1992).

    CAS  Article  Google Scholar 

  15. 15

    Mobley, H. L., Island, M. D. & Hausinger, R. P. Molecular biology of microbial ureases. Microbiol. Rev. 59, 451–480 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Skouloubris, S., Thiberge, J. M., Labigne, A. & De Reuse, H. The Helicobacter pylori UreI protein is not involved in urease activity but is essential for bacterial survival in vivo. Infect. Immun. 66, 4517–4521 ( 1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Weeks, D. L., Eskandari, S., Scott, D. R. & Sachs, G. A H+-gated urea channel: the link between Helicobacter pylori urease and gastritic colonization. Science 287 , 482–485 (2000).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Dong, Z., Onrust, R., Skangalis, M. & O'Donnell, M. DNA polymerase III accessory proteins. I. holA and holB encoding delta and delta′. J. Biol. Chem. 268, 11758– 11765 (1993).

    CAS  PubMed  Google Scholar 

  19. 19

    Liu, X. & Matsumura, P. An alternative sigma factor controls transcription of flagellar class-III operons in Escherichia coli: gene sequence, overproduction, purification and characterization. Gene 164, 81–84 ( 1995).

    CAS  Article  Google Scholar 

  20. 20

    Zhang, G. et al. Crystal structure of Thermus aquaticus core RNA polymerase at 3.3 A resolution. Cell 98, 811– 824 (1999).

    CAS  Article  Google Scholar 

  21. 21

    Mooney, R. A. & Landick, R. RNA polymerase unveiled. Cell 98, 687–690 ( 1999).

    CAS  Article  Google Scholar 

  22. 22

    Vidal, M. & Legrain, P. Yeast forward and reverse ‘n’-hybrid systems. Nucleic Acids Res. 27, 919– 929 (1999).

    CAS  Article  Google Scholar 

  23. 23

    Ferrero, R. L., Cussac, V., Courcoux, P. & Labigne, A. Construction of isogenic urease-negative mutants of Helicobacter pylori by allelic exchange. J. Bacteriol. 174, 4212– 4217 (1992).

    CAS  Article  Google Scholar 

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We thank M. Fromont-Racine, P. Glaser, A. Jacquier, A. Brunet and L. Decourty for their help at the launch of this project; M. Fejes, G. Conan and P. Desmoucelle for technical assistance; G. Boissy and J.-L. Divol for their help in software development; F. Colland for his contribution to the mapping of FliA interacting domain on the 3D structure of the core RNA polymerase; and S. Whiteside for a thorough and critical reading of the manuscript. We are very grateful to R. Benarous, J. Camonis, L. Daviet, M. Rosbash, A.D. Strosberg and S. Whiteside for many stimulating discussions. This work was supported by an interest-free loan from the ANVAR. P.L. is on leave from the CNRS.

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Correspondence to Pierre Legrain.

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Rain, JC., Selig, L., De Reuse, H. et al. The protein–protein interaction map of Helicobacter pylori. Nature 409, 211–215 (2001).

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