The Experts below are selected from a list of 27 Experts worldwide ranked by ideXlab platform
Martin L Privalsky - One of the best experts on this subject based on the ideXlab platform.
-
isotype restricted corepressor recruitment a constitutively closed helix 12 conformation in retinoic acid receptors β and γ interferes with corepressor recruitment and prevents transcriptional repression
Molecular and Cellular Biology, 2003Co-Authors: Behnom Farboud, Herborg Hauksdottir, Yun Wu, Martin L PrivalskyAbstract:Retinoic acid receptors (RARs) are ligand-regulated transcription factors that play multiple roles in vertebrate development and differentiation. RARs as a class are capable of both repressing and activating target gene expression. Transcriptional repression is mediated through the recruitment of corepressor proteins such as SMRT. Notably, vertebrates encode three major forms of RARs, α, β, and γ, and these distinct RAR isotypes differ in the ability to recruit a corepressor. RARα strongly interacts with SMRT and can repress target gene transcription, whereas RARβ and -γ interact with SMRT only weakly and fail to repress. We report here the use of a genetic suppressor approach, based on a yeast two-hybrid interaction assay using Saccharomyces cerevisiae, for the isolation of RARβ mutants that have gained the RARα-like corepressor phenotype, i.e., a strong interaction with SMRT and the ability to repress gene expression in vertebrate cells. Analysis of these gain-of-function mutants indicates that the different corepressor interaction properties of RARα, -β and -γ are determined by a gating mechanism through which amino acid differences in the helix 3 region of these receptors influence the position of the receptor C-terminal helix 12 domain. As a consequence, the RARβ and RARγ receptors appear to adopt a constitutively closed helix 12 conformation in the absence of hormone that may approximate the conformation of RARα when bound to hormone agonist. This closed helix 12 conformation in RARβ and RARγ blocks corepressor binding, prevents repression, and permits significant levels of target gene activation even in the absence of hormone. We refer to this phenomenon as a “Gate-Latch” model of corepressor regulation.
Edward X Zhou - One of the best experts on this subject based on the ideXlab platform.
-
structure determination and activity manipulation of the turfgrass aba receptor fepyr1
Scientific Reports, 2017Co-Authors: Zhizhong Ren, Edward X Zhou, Zhen Wang, Huazhong Shi, Yechun Hong, Minjie Cao, Zhulong Chan, Xue Liu, Jiankang ZhuAbstract:Turfgrass are widely cultivated ornamental plants that have important ecological, societal and economical values. However, many turfgrass species are susceptible to drought and demand frequent irrigation thus consuming large amounts of water. With the ultimate goal of improving drought resistance in turfgrass, we identified several ABA receptors in turfgrass that are important to mediate ABA signaling and drought stress response. The ABA receptor FePYR1 from turfgrass Festuca elata was demonstrated to bind ABA as a monomer. Crystal structure analysis revealed that FePYR1 recognizes and binds ABA by the common Gate-Latch-lock mechanism resembling the Arabidopsis ABA receptors, but the ABA binding pocket in FePYR1 shows discrepant residues resulting in different binding affinity to ABA. Structure-guided alterations of amino acid residues in FePYR1 generated ABA receptor variants with significantly increased ABA binding affinity. Expression of FePYR1 in Arabidopsis conferred enhanced drought resistance in the transgenic plants. These findings provided detailed information about FePYR1 and demonstrated that structure-assisted engineering could create superior ABA receptors for improving plant drought resistance. The detailed structural information of FePYR1 would also assist future rational design of small molecules targeting specific ABA receptors in economically important plant species.
-
an aba mimicking ligand that reduces water loss and promotes drought resistance in plants
Cell Research, 2013Co-Authors: Minjie Cao, Karsten Melcher, Edward X Zhou, Xue Liu, Yan Zhang, Xiaoqian Xue, Pan Gao, Fuxing Wang, Liang ZengAbstract:Abscisic acid (ABA) is the most important hormone for plants to resist drought and other abiotic stresses. ABA binds directly to the PYR/PYL family of ABA receptors, resulting in inhibition of type 2C phosphatases (PP2C) and activation of downstream ABA signaling. It is envisioned that intervention of ABA signaling by small molecules could help plants to overcome abiotic stresses such as drought, cold and soil salinity. However, chemical instability and rapid catabolism by plant enzymes limit the practical application of ABA itself. Here we report the identification of a small molecule ABA mimic (AM1) that acts as a potent activator of multiple members of the family of ABA receptors. In Arabidopsis, AM1 activates a gene network that is highly similar to that induced by ABA. Treatments with AM1 inhibit seed germination, prevent leaf water loss, and promote drought resistance. We solved the crystal structure of AM1 in complex with the PYL2 ABA receptor and the HAB1 PP2C, which revealed that AM1 mediates a Gate-Latch-lock interacting network, a structural feature that is conserved in the ABA-bound receptor/PP2C complex. Together, these results demonstrate that a single small molecule ABA mimic can activate multiple ABA receptors and protect plants from water loss and drought stress. Moreover, the AM1 complex crystal structure provides a structural basis for designing the next generation of ABA-mimicking small molecules.
-
a Gate Latch lock mechanism for hormone signalling by abscisic acid receptors
Nature, 2009Co-Authors: Karsten Melcher, Edward X Zhou, F F Soon, Kelly Suinopowell, Sangyoul Park, Joshua J Weiner, Hiroaki Fujii, Viswanathan ChinnusamyAbstract:Abscisic acid (ABA) is a ubiquitous hormone that regulates plant growth, development and responses to environmental stresses. Its action is mediated by the PYR/PYL/RCAR family of START proteins, but it remains unclear how these receptors bind ABA and, in turn, how hormone binding leads to inhibition of the downstream type 2C protein phosphatase (PP2C) effectors. Here we report crystal structures of apo and ABA-bound receptors as well as a ternary PYL2-ABA-PP2C complex. The apo receptors contain an open ligand-binding pocket flanked by a Gate that closes in response to ABA by way of conformational changes in two highly conserved beta-loops that serve as a Gate and Latch. Moreover, ABA-induced closure of the Gate creates a surface that enables the receptor to dock into and competitively inhibit the PP2C active site. A conserved tryptophan in the PP2C inserts directly between the Gate and Latch, which functions to further lock the receptor in a closed conformation. Together, our results identify a conserved Gate-Latch-lock mechanism underlying ABA signalling.
Behnom Farboud - One of the best experts on this subject based on the ideXlab platform.
-
isotype restricted corepressor recruitment a constitutively closed helix 12 conformation in retinoic acid receptors β and γ interferes with corepressor recruitment and prevents transcriptional repression
Molecular and Cellular Biology, 2003Co-Authors: Behnom Farboud, Herborg Hauksdottir, Yun Wu, Martin L PrivalskyAbstract:Retinoic acid receptors (RARs) are ligand-regulated transcription factors that play multiple roles in vertebrate development and differentiation. RARs as a class are capable of both repressing and activating target gene expression. Transcriptional repression is mediated through the recruitment of corepressor proteins such as SMRT. Notably, vertebrates encode three major forms of RARs, α, β, and γ, and these distinct RAR isotypes differ in the ability to recruit a corepressor. RARα strongly interacts with SMRT and can repress target gene transcription, whereas RARβ and -γ interact with SMRT only weakly and fail to repress. We report here the use of a genetic suppressor approach, based on a yeast two-hybrid interaction assay using Saccharomyces cerevisiae, for the isolation of RARβ mutants that have gained the RARα-like corepressor phenotype, i.e., a strong interaction with SMRT and the ability to repress gene expression in vertebrate cells. Analysis of these gain-of-function mutants indicates that the different corepressor interaction properties of RARα, -β and -γ are determined by a gating mechanism through which amino acid differences in the helix 3 region of these receptors influence the position of the receptor C-terminal helix 12 domain. As a consequence, the RARβ and RARγ receptors appear to adopt a constitutively closed helix 12 conformation in the absence of hormone that may approximate the conformation of RARα when bound to hormone agonist. This closed helix 12 conformation in RARβ and RARγ blocks corepressor binding, prevents repression, and permits significant levels of target gene activation even in the absence of hormone. We refer to this phenomenon as a “Gate-Latch” model of corepressor regulation.
Karsten Melcher - One of the best experts on this subject based on the ideXlab platform.
-
an aba mimicking ligand that reduces water loss and promotes drought resistance in plants
Cell Research, 2013Co-Authors: Minjie Cao, Karsten Melcher, Edward X Zhou, Xue Liu, Yan Zhang, Xiaoqian Xue, Pan Gao, Fuxing Wang, Liang ZengAbstract:Abscisic acid (ABA) is the most important hormone for plants to resist drought and other abiotic stresses. ABA binds directly to the PYR/PYL family of ABA receptors, resulting in inhibition of type 2C phosphatases (PP2C) and activation of downstream ABA signaling. It is envisioned that intervention of ABA signaling by small molecules could help plants to overcome abiotic stresses such as drought, cold and soil salinity. However, chemical instability and rapid catabolism by plant enzymes limit the practical application of ABA itself. Here we report the identification of a small molecule ABA mimic (AM1) that acts as a potent activator of multiple members of the family of ABA receptors. In Arabidopsis, AM1 activates a gene network that is highly similar to that induced by ABA. Treatments with AM1 inhibit seed germination, prevent leaf water loss, and promote drought resistance. We solved the crystal structure of AM1 in complex with the PYL2 ABA receptor and the HAB1 PP2C, which revealed that AM1 mediates a Gate-Latch-lock interacting network, a structural feature that is conserved in the ABA-bound receptor/PP2C complex. Together, these results demonstrate that a single small molecule ABA mimic can activate multiple ABA receptors and protect plants from water loss and drought stress. Moreover, the AM1 complex crystal structure provides a structural basis for designing the next generation of ABA-mimicking small molecules.
-
a Gate Latch lock mechanism for hormone signalling by abscisic acid receptors
Nature, 2009Co-Authors: Karsten Melcher, Edward X Zhou, F F Soon, Kelly Suinopowell, Sangyoul Park, Joshua J Weiner, Hiroaki Fujii, Viswanathan ChinnusamyAbstract:Abscisic acid (ABA) is a ubiquitous hormone that regulates plant growth, development and responses to environmental stresses. Its action is mediated by the PYR/PYL/RCAR family of START proteins, but it remains unclear how these receptors bind ABA and, in turn, how hormone binding leads to inhibition of the downstream type 2C protein phosphatase (PP2C) effectors. Here we report crystal structures of apo and ABA-bound receptors as well as a ternary PYL2-ABA-PP2C complex. The apo receptors contain an open ligand-binding pocket flanked by a Gate that closes in response to ABA by way of conformational changes in two highly conserved beta-loops that serve as a Gate and Latch. Moreover, ABA-induced closure of the Gate creates a surface that enables the receptor to dock into and competitively inhibit the PP2C active site. A conserved tryptophan in the PP2C inserts directly between the Gate and Latch, which functions to further lock the receptor in a closed conformation. Together, our results identify a conserved Gate-Latch-lock mechanism underlying ABA signalling.
Viswanathan Chinnusamy - One of the best experts on this subject based on the ideXlab platform.
-
a Gate Latch lock mechanism for hormone signalling by abscisic acid receptors
Nature, 2009Co-Authors: Karsten Melcher, Edward X Zhou, F F Soon, Kelly Suinopowell, Sangyoul Park, Joshua J Weiner, Hiroaki Fujii, Viswanathan ChinnusamyAbstract:Abscisic acid (ABA) is a ubiquitous hormone that regulates plant growth, development and responses to environmental stresses. Its action is mediated by the PYR/PYL/RCAR family of START proteins, but it remains unclear how these receptors bind ABA and, in turn, how hormone binding leads to inhibition of the downstream type 2C protein phosphatase (PP2C) effectors. Here we report crystal structures of apo and ABA-bound receptors as well as a ternary PYL2-ABA-PP2C complex. The apo receptors contain an open ligand-binding pocket flanked by a Gate that closes in response to ABA by way of conformational changes in two highly conserved beta-loops that serve as a Gate and Latch. Moreover, ABA-induced closure of the Gate creates a surface that enables the receptor to dock into and competitively inhibit the PP2C active site. A conserved tryptophan in the PP2C inserts directly between the Gate and Latch, which functions to further lock the receptor in a closed conformation. Together, our results identify a conserved Gate-Latch-lock mechanism underlying ABA signalling.