Structural basis of steroid hormone perception by the receptor kinase BRI1

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Polyhydroxylated steroids are regulators of body shape and size in higher organisms. In metazoans, intracellular receptors recognize these molecules. Plants, however, perceive steroids at membranes, using the membrane-integral receptor kinase BRASSINOSTEROID INSENSITIVE 1 (BRI1). Here we report the structure of the Arabidopsis thaliana BRI1 ligand-binding domain, determined by X-ray diffraction at 2.5 Å resolution. We find a superhelix of 25 twisted leucine-rich repeats (LRRs), an architecture that is strikingly different from the assembly of LRRs in animal Toll-like receptors. A 70-amino-acid island domain between LRRs 21 and 22 folds back into the interior of the superhelix to create a surface pocket for binding the plant hormone brassinolide. Known loss- and gain-of-function mutations map closely to the hormone-binding site. We propose that steroid binding to BRI1 generates a docking platform for a co-receptor that is required for receptor activation. Our findings provide insight into the activation mechanism of this highly expanded family of plant receptors that have essential roles in hormone, developmental and innate immunity signalling.

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Figure 1: The BRI1 ectodomain forms a superhelix.
Figure 2: Plant-specific sequence fingerprints cause the superhelical arrangement.
Figure 3: The steroid hormone binding site maps to the C-terminal inner surface of the superhelix.
Figure 4: An accessible membrane-proximal region of BRI1 may provide a protein–protein interaction platform.

Accession codes

Primary accessions

Protein Data Bank

Data deposits

Atomic coordinates and structure factors for the reported crystal structures have been deposited in the Protein Data Bank under accession numbers 3RIZ for the unliganded BRI1 ectodomain and 3RJ0 for the BRI1–brassinolide complex.


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We thank J. Vanhnasy and W. Yu for maintaining insect cell stocks, M. Jinek and B. W. Han for advice, W. Kwiatowski for maintenance of the Salk X-ray equipment, Y. Jaillais for discussion, and F. V. Chisari for encouragement and support. This work was supported by the Howard Hughes Medical Institute and a grant from the National Science Foundation (IOS-0649389) to J.C. M.H. was supported by long-term fellowships from the European Molecular Biology Organisation and the International Human Frontier Science Program Organisation. Y.B. was a Howard Hughes Medical Institute fellow of the Life Sciences Research Foundation and also received support from the Philippe Foundation. I.A.W. was supported by NIH grant AI042266 and by the Skaggs Institute for Chemical Biology.

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M.H., Y.B., J.P.N. and J.C. designed the project. M.H. expressed the BRI1 ectodomain in the laboratory of I.A.W. with initial help from Y.B. M.H. purified and crystallized the protein, and phased and refined the structures. M.D. determined viral titres and optimized production of viruses. T.D. cloned the modified transfer vector. M.H., I.A.W. and J.C. analysed the data. J.C. supervised the project. M.H. wrote the paper with input from the other authors.

Correspondence to Joanne Chory.

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Hothorn, M., Belkhadir, Y., Dreux, M. et al. Structural basis of steroid hormone perception by the receptor kinase BRI1. Nature 474, 467–471 (2011) doi:10.1038/nature10153

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