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Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins

Nature volume 403, pages 567–571 (2000)Cite this article

Abstract

Interferon-γ is an immunomodulatory substance that induces the expression of many genes to orchestrate a cellular response and establish the antiviral state of the cell. Among the most abundant antiviral proteins induced by interferon-γ are guanylate-binding proteins such as GBP1 and GBP2 (refs 1, 2). These are large GTP-binding proteins of relative molecular mass 67,000 with a high-turnover GTPase activity3 and an antiviral effect4. Here we have determined the crystal structure of full-length human GBP1 to 1.8 Å resolution. The amino-terminal 278 residues constitute a modified G domain with a number of insertions compared to the canonical Ras structure, and the carboxy-terminal part is an extended helical domain with unique features. From the structure and biochemical experiments reported here, GBP1 appears to belong to the group of large GTP-binding proteins that includes Mx and dynamin, the common property of which is the ability to undergo oligomerization with a high concentration-dependent GTPase activity5.

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Figure 1: Primary, secondary and tertiary structure of hGBP1.
Figure 2: Comparison of hGBP1 and Ras structures.
Figure 3: Interaction of the C-terminal helix motif α12/13 with the helical and the LG domains.
Figure 4: Cooperative GTP hydrolysis and nucleotide-dependent multimerization of hGBP1.

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Acknowledgements

The work was supported by the Deutsche Forschungsgemeinschaft (C.H.) and by Boehringer Ingelheim Fonds (G.J.K.P). We thank the staff at beamlines BW6, DESY, Hamburg and at BM-14, ESRF, Grenoble for help with data collection. We also thank I. Schlichting, I. Vetter and R. Hillig for discussions and M. Hess for help with figures. A. Beste for help with HPLC and R. Schebaum for secretarial assistance.

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Author notes

  1. Balaji Prakash, Gerrit J. K. Praefcke and Christian Herrmann: These authors contributed equally to this work

  2. Correspondence and requests for materials should be addressed to A.W. or to C.H. Coordinates have been deposited with the Protein Data Bank (accession no. 1DG3).

Authors and Affiliations

  1. Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Strasse 11, Dortmund, 44227, Germany

    Balaji Prakash, Gerrit J. K. Praefcke, Louis Renault,  Alfred Wittinghofer & Christian Herrmann

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Prakash, B., Praefcke, G., Renault, L. et al. Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins. Nature 403, 567–571 (2000). https://doi.org/10.1038/35000617

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