title: Structural basis for recognition of diverse transcriptional repressors by the TOPLESS family of corepressors.
abstract: TOPLESS (TPL) and TOPLESS-related (TPR) proteins comprise a conserved family of plant transcriptional corepressors that are related to Tup1, Groucho, and TLE (transducin-like enhancer of split) corepressors in yeast, insects, and mammals. In plants, TPL/TPR corepressors regulate development, stress responses, and hormone signaling through interaction with small ethylene response factor-associated amphiphilic repression (EAR) motifs found in diverse transcriptional repressors. How EAR motifs can interact with TPL/TPR proteins is unknown. We confirm the amino-terminal domain of the TPL family of corepressors, which we term TOPLESS domain (TPD), as the EAR motif-binding domain. To understand the structural basis of this interaction, we determined the crystal structures of the TPD of rice (Os) TPR2 in apo (apo protein) state and in complexes with the EAR motifs from Arabidopsis NINJA (novel interactor of JAZ), IAA1 (auxin-responsive protein 1), and IAA10, key transcriptional repressors involved in jasmonate and auxin signaling. The OsTPR2 TPD adopts a new fold of nine helices, followed by a zinc finger, which are arranged into a disc-like tetramer. The EAR motifs in the three different complexes adopt a similar extended conformation with the hydrophobic residues fitting into the same surface groove of each OsTPR2 monomer. Sequence alignments and structure-based mutagenesis indicate that this mode of corepressor binding is highly conserved in a large set of transcriptional repressors, thus providing a general mechanism for gene repression mediated by the TPL family of corepressors.
authors.affiliation: Key Laboratory of Receptor Research, VARI-SIMM Center, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China. ; Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503, USA.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Ke
authors.affiliation: Key Laboratory of Receptor Research, VARI-SIMM Center, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China. ; Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503, USA.
authors.forename: Honglei
authors.initials: H
authors.lastname: Ma
authors.affiliation: Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Gu
authors.affiliation: Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Thelen
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Life Sciences Collaborative Access Team, Synchrotron Research Center, Northwestern University, Argonne, IL 60439, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Brunzelle
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, People's Republic of China.
authors.forename: Jiayang
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Receptor Research, VARI-SIMM Center, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China. ; Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503, USA.
authors.forename: H Eric
authors.initials: HE
authors.lastname: Xu
authors.affiliation: Key Laboratory of Receptor Research, VARI-SIMM Center, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China. ; Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503, USA.
authors.forename: Karsten
authors.initials: K
authors.lastname: Melcher
keywords: EAR; Groucho; IAA; NINJA; TLE; TPD; TPR; TUP1; Topless; auxin; jasmonate