Mechanism of auxin perception by the TIR1 ubiquitin ligase.
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.
Tan
Xu
X
Department of Pharmacology, University of Washington, School of Medicine, Box 357280, Seattle, Washington 98195, USA.
Calderon-Villalobos
Luz Irina A
LI
Sharon
Michal
M
Zheng
Changxue
C
Robinson
Carol V
CV
Estelle
Mark
M
Zheng
Ning
N
D017360:Arabidopsis / Q000201:enzymology / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D044783:F-Box Proteins / Q000737:chemistry* / Q000378:metabolism*; D007210:Indoleacetic Acids / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010833:Phytic Acid / Q000378:metabolism; D010937:Plant Growth Regulators / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000378:metabolism*
C120363:ASK1 protein, Arabidopsis; D029681:Arabidopsis Proteins; D044783:F-Box Proteins; D007210:Indoleacetic Acids; D010937:Plant Growth Regulators; D011956:Receptors, Cell Surface; C501405:TIR1 protein, Arabidopsis; D010833:Phytic Acid; D044767:Ubiquitin-Protein Ligases