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Structural basis for selective activation of ABA receptors

Nature Structural & Molecular Biology volume 17, pages 1109–1113 (2010)Cite this article

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Abstract

Changing environmental conditions and lessening fresh water supplies have sparked intense interest in understanding and manipulating abscisic acid (ABA) signaling, which controls adaptive responses to drought and other abiotic stressors. We recently discovered a selective ABA agonist, pyrabactin, and used it to discover its primary target PYR1, the founding member of the PYR/PYL family of soluble ABA receptors. To understand pyrabactin's selectivity, we have taken a combined structural, chemical and genetic approach. We show that subtle differences between receptor binding pockets control ligand orientation between productive and nonproductive modes. Nonproductive binding occurs without gate closure and prevents receptor activation. Observations in solution show that these orientations are in rapid equilibrium that can be shifted by mutations to control maximal agonist activity. Our results provide a robust framework for the design of new agonists and reveal a new mechanism for agonist selectivity.

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Figure 1: Pyrabactin binds the ABA binding pocket of PYR1 and induces gate closure.
Figure 2: Crystal structure of the PYL2–pyrabactin complex.
Figure 3: Genetic identification of pyrabactin selectivity determinants.
Figure 4: Ligand orientation polymorphisms underlie selectivity.

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Acknowledgements

S.R.C. thanks Jeffrey Bachant (Univ. of California, Riverside) for sharing yeast strains. This work was supported by the US National Institute of General Medical Sciences Protein Structure Initiative (U54 GM074901) and the US National Science Foundation (IOS-003725-002). We acknowledge the Life Sciences Collaborative Access Team at sector 21 at the Advanced Photon Source at Argonne National Laboratory for X-ray beamline access.

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Author notes

  1. Francis C Peterson and E Sethe Burgie: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Center for Eukaryotic Structural Genomics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    Francis C Peterson, Davin R Jensen, Joshua J Weiner & Brian F Volkman

  2. Department of Biochemistry and Center for Eukaryotic Structural Genomics, University of Wisconsin-Madison, Madison, Wisconsin, USA

    E Sethe Burgie, Craig A Bingman & George N Phillips Jr

  3. Department of Botany and Plant Sciences and the Center for Plant Cell Biology, University of California-Riverside, Riverside, California, USA

    Sang-Youl Park & Sean R Cutler

  4. Department of Chemistry, University of California-Riverside, Riverside, California, USA

    Chia-En A Chang & Sean R Cutler

Authors
  1. Francis C Peterson
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Contributions

F.C.P., E.S.B. and C.A.B. solved crystal structures; S.-Y.P. performed assays and carried out cloning of ABA receptors and mutagenesis studies; J.J.W. performed NMR analysis; D.R.J. purified proteins and contributed to crystallization screening; C.-A.C. performed modeling studies; G.N.P., S.R.C. and B.F.V. supervised the work, interpreted data and contributed to the writing of the manuscript.

Corresponding authors

Correspondence to Sean R Cutler, George N Phillips Jr or Brian F Volkman.

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Competing interests

S.R.C. holds a related patent application; the S.R.C. laboratory receives research funding from Syngenta.

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Supplementary Figures 1–3 and Supplementary Table 1 (PDF 462 kb)

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Peterson, F., Burgie, E., Park, SY. et al. Structural basis for selective activation of ABA receptors. Nat Struct Mol Biol 17, 1109–1113 (2010). https://doi.org/10.1038/nsmb.1898

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