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Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase

Nature Structural & Molecular Biology volume 15, pages 65–70 (2008)Cite this article

Abstract

Bacterial pathogens deliver virulence proteins into host cells to facilitate entry and survival. Salmonella SopA functions as an E3 ligase to manipulate the host proinflammatory response. Here we report the crystal structure of SopA in two conformations. Although it has little sequence similarity to eukaryotic HECT-domain E3s, the C-terminal half of SopA has a bilobal architecture that is reminiscent of the N- and C-lobe arrangement of HECT domains. The SopA structure also contains a putative substrate-binding domain located near the E2-binding site. The two structures of SopA differ in the relative orientations of the C lobe, indicating that SopA possesses the conformational flexibility essential for HECT E3 function. These results suggest that SopA is a unique HECT E3 ligase evolved from the coevolutionary selective pressure at the bacterium-host interface.

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Figure 1: E3 ligase activity of SopA.
Figure 2: SopA crystal structure.
Figure 3: Conformational flexibility.
Figure 4: SopA-E2 interactions.
Figure 5: Comparison of bacterial and eukaryotic HECT E3 domains.

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Acknowledgements

We thank the staff at the Advanced Photon Source beam line 23-ID for assistance with data collection. This work was supported by US National Institutes of Health grants (AI049978 to D.Z. and CA072943 to J.M.H.) and by a Pew scholarship (to J.C.).

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Authors and Affiliations

  1. Department of Biological Sciences, Purdue University, West Lafayette, 47907, Indiana, USA

    Jianbo Diao, Ying Zhang, Daoguo Zhou & Jue Chen

  2. Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, 78712, Texas, USA

    Jon M Huibregtse

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  1. Jianbo Diao
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  2. Ying Zhang
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  3. Jon M Huibregtse
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  4. Daoguo Zhou
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Contributions

J.D. determined the structures of SopA and contributed the data for Figure 4a,b. Y.Z. subcloned most of the constructs and contributed the data for Figures 1 and 4c and Supplementary Figure 3. J.D., Y.Z., J.M.H., D.Z. and J.C. designed experiments, analyzed data and prepared the manuscript.

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Correspondence to Daoguo Zhou or Jue Chen.

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Diao, J., Zhang, Y., Huibregtse, J. et al. Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase. Nat Struct Mol Biol 15, 65–70 (2008). https://doi.org/10.1038/nsmb1346

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