title: Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3.
abstract: Strigolactones (SLs) are endogenous hormones and exuded signaling molecules in plant responses to low levels of mineral nutrients. Key mediators of the SL signaling pathway in rice include the α/β-fold hydrolase DWARF 14 (D14) and the F-box component DWARF 3 (D3) of the ubiquitin ligase SCF(D3) that mediate ligand-dependent degradation of downstream signaling repressors. One perplexing feature is that D14 not only functions as the SL receptor but is also an active enzyme that slowly hydrolyzes diverse natural and synthetic SLs including GR24, preventing the crystallization of a binary complex of D14 with an intact SL as well as the ternary D14/SL/D3 complex. Here we overcome these barriers to derive a structural model of D14 bound to intact GR24 and identify the interface that is required for GR24-mediated D14-D3 interaction. The mode of GR24-mediated signaling, including ligand recognition, hydrolysis by D14, and ligand-mediated D14-D3 interaction, is conserved in structurally diverse SLs. More importantly, D14 is destabilized upon the binding of ligands and D3, thus revealing an unusual mechanism of SL recognition and signaling, in which the hormone, the receptor, and the downstream effectors are systematically destabilized during the signal transduction process.
authors.affiliation: VARI-SIMM Center, Center for Structure and Function of Drug Targets, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zhao
authors.affiliation: Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, Grand Rapids, Michigan, USA.
authors.forename: X Edward
authors.initials: XE
authors.lastname: Zhou
authors.affiliation: VARI-SIMM Center, Center for Structure and Function of Drug Targets, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: VARI-SIMM Center, Center for Structure and Function of Drug Targets, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, Grand Rapids, Michigan, USA.|Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Hubei 430074, China.
authors.forename: Zhongshan
authors.initials: Z
authors.lastname: Wu
authors.affiliation: VARI-SIMM Center, Center for Structure and Function of Drug Targets, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, Grand Rapids, Michigan, USA.
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Kang
authors.affiliation: VARI-SIMM Center, Center for Structure and Function of Drug Targets, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, Grand Rapids, Michigan, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Hou
authors.affiliation: Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, Grand Rapids, Michigan, USA.
authors.forename: Parker W
authors.initials: PW
authors.lastname: de Waal
authors.affiliation: VARI-SIMM Center, Center for Structure and Function of Drug Targets, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Suling
authors.initials: S
authors.lastname: Li
authors.affiliation: VARI-SIMM Center, Center for Structure and Function of Drug Targets, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
authors.forename: Adrian
authors.initials: A
authors.lastname: Scaffidi
authors.affiliation: School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Flematti
authors.affiliation: School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.|School of Biological Sciences, University of Tasmania Hobart, Hobart, TAS 7001 Australia.|State Key Laboratory of Plant Genomics and National Center for Plant Gene Research (Beijing), Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: Department of Molecular Therapeutics, Translational Research Institute, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.
authors.forename: Vinh Q
authors.initials: VQ
authors.lastname: Lam
authors.affiliation: Department of Molecular Therapeutics, Translational Research Institute, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Griffin
authors.affiliation: State Key Laboratory of Plant Genomics and National Center for Plant Gene Research (Beijing), Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Plant Genomics and National Center for Plant Gene Research (Beijing), Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jiayang
authors.initials: J
authors.lastname: Li
authors.affiliation: VARI-SIMM Center, Center for Structure and Function of Drug Targets, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, Grand Rapids, Michigan, USA.
authors.forename: Karsten
authors.initials: K
authors.lastname: Melcher
authors.affiliation: VARI-SIMM Center, Center for Structure and Function of Drug Targets, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, Grand Rapids, Michigan, USA.
authors.forename: H Eric
authors.initials: HE
authors.lastname: Xu
mesh_terms: D006575:Heterocyclic Compounds, 3-Ring / Q000378:metabolism*; D007783:Lactones / Q000378:metabolism*; D012275:Oryza / Q000378:metabolism*; D010937:Plant Growth Regulators / Q000737:chemistry / Q000378:metabolism*; D010940:Plant Proteins / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C000591191:GR24 strigolactone; D006575:Heterocyclic Compounds, 3-Ring; D007783:Lactones; D010937:Plant Growth Regulators; D010940:Plant Proteins; D044843:SKP Cullin F-Box Protein Ligases