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A novel two-chain proteinase inhibitor generated by circularization of a multidomain precursor protein

Nature Structural Biology volume 6, pages 526–530 (1999)Cite this article

Abstract

Female reproductive tissues of the ornamental tobacco amass high levels of serine proteinase inhibitors (PIs) for protection against pests and pathogens. These PIs are produced from a precursor protein composed of six repeats each with a protease reactive site. Here we show that proteolytic processing of the precursor generates five single-chain PIs and a remarkable two-chain inhibitor formed by disulfide-bond linkage of N- and C-terminal peptide fragments. Surprisingly, PI precursors adopt this circular structure regardless of the number of inhibitor domains, suggesting this bracelet-like conformation is characteristic of the widespread potato inhibitor II (Pot II) protein family.

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Figure 1: Isolation of the two-chain inhibitor, C2.
Figure 2: NMR structure of C2.
Figure 3: Model of Na-PI structure.
Figure 4: Ancestral PI.

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Acknowledgements

We thank G.M. Neumann and R. Condron for electrospray mass spectrometry and N-terminal sequencing analysis, and E.A. Miller, T.J. Lithgow, N.J. Hoogenraad and A.E. Clarke for critical reading of the manuscript. This work was supported by a grant from the Australian Research Council. D.J.C. is an Australian Research Council Senior Fellow.

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Authors and Affiliations

  1. School of Biochemistry, La Trobe University, Bundoora, 3083, Victoria, Australia

    Marcus C.S. Lee & Marilyn A. Anderson

  2. Plant Cell Biology Research Centre, School of Botany, University of Melbourne, Parkville, 3052, Victoria, Australia

    Marcus C.S. Lee

  3. Centre for Drug Design and Development, University of Queensland, St. Lucia, 4072, Queensland, Australia

    Martin J. Scanlon & David J. Craik

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  1. Marcus C.S. Lee
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  2. Martin J. Scanlon
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  4. Marilyn A. Anderson
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Correspondence to Marilyn A. Anderson.

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Lee, M., Scanlon, M., Craik, D. et al. A novel two-chain proteinase inhibitor generated by circularization of a multidomain precursor protein. Nat Struct Mol Biol 6, 526–530 (1999). https://doi.org/10.1038/9293

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