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. The brassinolides are potent steroid hormones that are central to plant growth and development. They bind to the plasma membrane receptor BRI1, a member of the leucine-rich repeat (LRR) receptor family that also includes the mammalian Toll-like receptors, which are important in innate immunity. Two independent studies now present the crystal structure of BRI1 from Arabidopsis thaliana, both in the free form and in complex with brassinolide. BRI1 is found to adopt a solenoid-like superhelical structure involving 25 leucine-rich repeats. The structure is strikingly different from that of Toll-like receptors and reveals a novel mechanism of steroid recognition. This work suggests synthetic routes to nonsteroidal mimetics of BRI1 that could have a possible use in agriculture.

Structural basis of steroid hormone perception by the receptor kinase BRI1