Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3

Cell Research (2015) 25:1219-1236. 2015 IBCB, SIBS, CAS All rights reserved 1001-0602/15 $ 32.00 www.nature.com/cr

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ORIGINAL ARTICLE

Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3

Li-Hua Zhao1, 2, *, X Edward Zhou3, *, Wei Yi1, *, Zhongshan Wu1, 3, 4, Yue Liu1, Yanyong Kang3, Li Hou1, 3,Parker W de Waal3, Suling Li1, Yi Jiang1, Adrian Scafdi5, Gavin R Flematti5, Steven M Smith5, 6, 7, Vinh Q Lam8, Patrick R Grifn8, Yonghong Wang7, Jiayang Li7, Karsten Melcher1, 3, H Eric Xu1, 3

1VARI-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; 2The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241; 3Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, Grand Rapids, Michigan, USA; 4Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Hubei 430074, China; 5School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia; 6School of Biological Sciences, University of Tasmania Hobart, Hobart, TAS 7001 Australia; 7State 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; 8Department of Molecular Therapeutics, Translational Research Institute, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA

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 /-fold hydrolase DWARF 14 (D14) and the F-box component DWARF 3 (D3) of the ubiquitin ligase SCFD3 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...