Article

Mechanism of auxin perception by the TIR1 ubiquitin ligase

  • Nature volume 446, pages 640645 (05 April 2007)
  • doi:10.1038/nature05731
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Abstract

Auxin is a pivotal plant hormone that controls many aspects of plant growth and development. Perceived by a small family of F-box proteins including transport inhibitor response 1 (TIR1), auxin regulates gene expression by promoting SCF ubiquitin-ligase-catalysed degradation of the Aux/IAA transcription repressors, but how the TIR1 F-box protein senses and becomes activated by auxin remains unclear. Here we present the crystal structures of the Arabidopsis TIR1–ASK1 complex, free and in complexes with three different auxin compounds and an Aux/IAA substrate peptide. These structures show that the leucine-rich repeat domain of TIR1 contains an unexpected inositol hexakisphosphate co-factor and recognizes auxin and the Aux/IAA polypeptide substrate through a single surface pocket. Anchored to the base of the TIR1 pocket, auxin binds to a partially promiscuous site, which can also accommodate various auxin analogues. Docked on top of auxin, the Aux/IAA substrate peptide occupies the rest of the TIR1 pocket and completely encloses the hormone-binding site. By filling in a hydrophobic cavity at the protein interface, auxin enhances the TIR1–substrate interactions by acting as a ‘molecular glue’. Our results establish the first structural model of a plant hormone receptor.

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Acknowledgements

We thank the beamline staff of the Advanced Light Source at Berkeley for help with data collection. We also thank J. Callis, W. Xu and members of the Zheng laboratory for discussions and help. This work is supported by grants from the National Institutes of Health (M.E), the Pew Scholar Program (N.Z.), the National Science Foundation (M.E.) and the Department of Energy (M.E.).

Structure coordinates and structural factors are deposited in the Protein Data Bank under accession numbers 2P1M, 2P1N, 2P1O, 2P1P and 2P1Q (see Supplementary Table 1).

Author information

Affiliations

  1. Department of Pharmacology, University of Washington, School of Medicine, Box 357280, Seattle, Washington 98195, USA

    • Xu Tan
    • , Changxue Zheng
    •  & Ning Zheng
  2. Department of Biology, Indiana University, Bloomington, Indiana 47405, USA

    • Luz Irina A. Calderon-Villalobos
    •  & Mark Estelle
  3. Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK

    • Michal Sharon
    •  & Carol V. Robinson

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Competing interests

Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Corresponding author

Correspondence to Ning Zheng.

Supplementary information

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  1. 1.

    Supplementary Information

    This file contains Supplementary Figures 1-7 with Legends, Supplementary Table 1 and additional references.

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