The Experts below are selected from a list of 1782 Experts worldwide ranked by ideXlab platform
Josephine C Adams - One of the best experts on this subject based on the ideXlab platform.
-
Molecular analysis of muskelin identifies a conserved discoidin-like domain that contributes to protein self-association
Biochemical Journal, 2004Co-Authors: Soren Prag, Georgina D. M. Collett, Josephine C AdamsAbstract:Muskelin is an intracellular protein with a C-terminal Kelch-Repeat domain that was initially characterized as having functional involvement in cell spreading on the extracellular matrix glycoprotein thrombospondin-1. As one approach to understanding the functional properties of muskelin, we have combined bioinformatic and biochemical studies. Through analysis of a new dataset of eight animal muskelins, we showed that the N-terminal region of the polypeptide corresponds to a predicted discoidin-like domain. This domain architecture is conserved in fungal muskelins and reveals a structural parallel between the muskelins and certain extracellular fungal galactose oxidases, although the phylogeny of the two groups appears distinct. In view of the fact that a number of Kelch-Repeat proteins have been shown to self-associate, co-immunoprecipitation, protein pull-down assays and studies of cellular localization were carried out with wild-type, deletion mutant and point mutant muskelins to investigate the roles of the discoidin-like and Kelch-Repeat domains. We obtained evidence for cis- and trans-interactions between the two domains. These studies provide evidence that muskelin self-associates through a head-to-tail mechanism involving the discoidin-like domain.
-
molecular phylogeny of the Kelch Repeat superfamily reveals an expansion of btb Kelch proteins in animals
BMC Bioinformatics, 2003Co-Authors: Soren Prag, Josephine C AdamsAbstract:Background The Kelch motif is an ancient and evolutionarily-widespread sequence motif of 44–56 amino acids in length. It occurs as five to seven Repeats that form a β-propeller tertiary structure. Over 28 Kelch-Repeat proteins have been sequenced and functionally characterised from diverse organisms spanning from viruses, plants and fungi to mammals and it is evident from expressed sequence tag, domain and genome databases that many additional hypothetical proteins contain Kelch-Repeats. In general, Kelch-Repeat β-propellers are involved in protein-protein interactions, however the modest sequence identity between Kelch motifs, the diversity of domain architectures, and the partial information on this protein family in any single species, all present difficulties to developing a coherent view of the Kelch-Repeat domain and the Kelch-Repeat protein superfamily. To understand the complexity of this superfamily of proteins, we have analysed by bioinformatics the complement of Kelch-Repeat proteins encoded in the human genome and have made comparisons to the Kelch-Repeat proteins encoded in other sequenced genomes.
-
Molecular phylogeny of the Kelch-Repeat superfamily reveals an expansion of BTB/Kelch proteins in animals
BMC Bioinformatics, 2003Co-Authors: Soren Prag, Josephine C AdamsAbstract:Background The Kelch motif is an ancient and evolutionarily-widespread sequence motif of 44–56 amino acids in length. It occurs as five to seven Repeats that form a β-propeller tertiary structure. Over 28 Kelch-Repeat proteins have been sequenced and functionally characterised from diverse organisms spanning from viruses, plants and fungi to mammals and it is evident from expressed sequence tag, domain and genome databases that many additional hypothetical proteins contain Kelch-Repeats. In general, Kelch-Repeat β-propellers are involved in protein-protein interactions, however the modest sequence identity between Kelch motifs, the diversity of domain architectures, and the partial information on this protein family in any single species, all present difficulties to developing a coherent view of the Kelch-Repeat domain and the Kelch-Repeat protein superfamily. To understand the complexity of this superfamily of proteins, we have analysed by bioinformatics the complement of Kelch-Repeat proteins encoded in the human genome and have made comparisons to the Kelch-Repeat proteins encoded in other sequenced genomes. Results We identified 71 Kelch-Repeat proteins encoded in the human genome, whereas 5 or 8 members were identified in yeasts and around 18 in C. elegans , D. melanogaster and A. gambiae . Multiple domain architectures were identified in each organism, including previously unrecognised forms. The vast majority of Kelch-Repeat domains are predicted to form six-bladed β-propellers. The most prevalent domain architecture in the metazoan animal genomes studied was the BTB/Kelch domain organisation and we uncovered 3 subgroups of human BTB/Kelch proteins. Sequence analysis of the Kelch-Repeat domains of the most robustly-related subgroups identified differences in β-propeller organisation that could provide direction for experimental study of protein-binding characteristics. Conclusion The Kelch-Repeat superfamily constitutes a distinct and evolutionarily-widespread family of β-propeller domain-containing proteins. Expansion of the family during the evolution of multicellular animals is mainly accounted for by a major expansion of the BTB/Kelch domain architecture. BTB/Kelch proteins constitute 72 % of the Kelch-Repeat superfamily of H. sapiens and form three subgroups, one of which appears the most-conserved during evolution. Distinctions in propeller blade organisation between subgroups 1 and 2 were identified that could provide new direction for biochemical and functional studies of novel Kelch-Repeat proteins.
-
Molecular phylogeny of the Kelch-Repeat superfamily reveals an expansion of BTB/Kelch proteins in animals
BMC Bioinformatics, 2003Co-Authors: Soren Prag, Josephine C AdamsAbstract:Background The Kelch motif is an ancient and evolutionarily-widespread sequence motif of 44–56 amino acids in length. It occurs as five to seven Repeats that form a β-propeller tertiary structure. Over 28 Kelch-Repeat proteins have been sequenced and functionally characterised from diverse organisms spanning from viruses, plants and fungi to mammals and it is evident from expressed sequence tag, domain and genome databases that many additional hypothetical proteins contain Kelch-Repeats. In general, Kelch-Repeat β-propellers are involved in protein-protein interactions, however the modest sequence identity between Kelch motifs, the diversity of domain architectures, and the partial information on this protein family in any single species, all present difficulties to developing a coherent view of the Kelch-Repeat domain and the Kelch-Repeat protein superfamily. To understand the complexity of this superfamily of proteins, we have analysed by bioinformatics the complement of Kelch-Repeat proteins encoded in the human genome and have made comparisons to the Kelch-Repeat proteins encoded in other sequenced genomes.
-
The Kelch Repeat superfamily of proteins: propellers of cell function.
Trends in Cell Biology, 2000Co-Authors: Josephine C Adams, Reed J. Kelso, Lynn CooleyAbstract:Abstract The Kelch motif was discovered as a sixfold tandem element in the sequence of the Drosophila Kelch ORF1 protein. The Repeated Kelch motifs predict a conserved tertiary structure, a β-propeller. This module appears in many different polypeptide contexts and contains multiple potential protein–protein contact sites. Members of this growing superfamily are present throughout the cell and extracellularly and have diverse activities. In this review, we discuss current information concerning the structural organization of Kelch Repeat proteins, their biological roles and the molecular basis of their action.
Joseph Heitman - One of the best experts on this subject based on the ideXlab platform.
-
2005. G� subunit Gpa2 recruits Kelch Repeat subunits that inhibit receptor-G protein coupling during cAMP-induced dimorphic transitions in Saccharomyces cerevisiae. Mol. Biol. Cell 16:4557–4571
2013Co-Authors: Toshiaki Harashima, Joseph Heitman, Department Of Molecular GeneticsAbstract:All eukaryotic cells sense extracellular stimuli and activate intracellular signaling cascades via G protein-coupled receptors (GPCR) and associated heterotrimeric G proteins. The Saccharomyces cerevisiae GPCR Gpr1 and associated G� subunit Gpa2 sense extracellular carbon sources (including glucose) to govern filamentous growth. In contrast to conventional G � subunits, Gpa2 forms an atypical G protein complex with the Kelch Repeat G � mimic proteins Gpb1 and Gpb2. Gpb1/2 negatively regulate cAMP signaling by inhibiting Gpa2 and an as yet unidentified target. Here we show that Gpa2 requires lipid modifications of its N-terminus for membrane localization but association with the Gpr1 receptor or Gpb1/2 subunits is dispensable for membrane targeting. Instead, Gpa2 promotes membrane localization of its associated G � mimic subunit Gpb2. We also show that the Gpa2 N-terminus binds both to Gpb2 and to the C-terminal tail of the Gpr1 receptor and that Gpb1/2 binding interferes with Gpr1 receptor coupling to Gpa2. Our studies invoke novel mechanisms involving GPCR-G protein modules that may be conserved in multicellular eukaryotes. This article was published online ahead of print in MBC in Pres
-
Running Head; Novel heteromeric G protein signaling
2013Co-Authors: Toshiaki Harashima, Joseph Heitman, Key Words Heterotrimeric G Protein, Kelch Gβ Mimic Proteins, Yeast Dimorphic, Transition Gpa GpbAbstract:recruits Kelch Repeat subunits that inhibit receptor-G protei
-
Gα Subunit Gpa2 Recruits Kelch Repeat Subunits That Inhibit Receptor-G Protein Coupling during cAMP-induced Dimorphic Transitions in Saccharomyces cerevisiae
Molecular Biology of the Cell, 2005Co-Authors: Toshiaki Harashima, Joseph HeitmanAbstract:All eukaryotic cells sense extracellular stimuli and activate intracellular signaling cascades via G protein-coupled receptors (GPCR) and associated heterotrimeric G proteins. The Saccharomyces cerevisiae GPCR Gpr1 and associated Gα subunit Gpa2 sense extracellular carbon sources (including glucose) to govern filamentous growth. In contrast to conventional Gα subunits, Gpa2 forms an atypical G protein complex with the Kelch Repeat Gβ mimic proteins Gpb1 and Gpb2. Gpb1/2 negatively regulate cAMP signaling by inhibiting Gpa2 and an as yet unidentified target. Here we show that Gpa2 requires lipid modifications of its N-terminus for membrane localization but association with the Gpr1 receptor or Gpb1/2 subunits is dispensable for membrane targeting. Instead, Gpa2 promotes membrane localization of its associated Gβ mimic subunit Gpb2. We also show that the Gpa2 N-terminus binds both to Gpb2 and to the C-terminal tail of the Gpr1 receptor and that Gpb1/2 binding interferes with Gpr1 receptor coupling to Gpa2. Our studies invoke novel mechanisms involving GPCR-G protein modules that may be conserved in multicellular eukaryotes.
-
6 Nutrient control of dimorphic growth in Saccharomyces cerevisiae
Topics in Current Genetics, 2004Co-Authors: Toshiaki Harashima, Joseph HeitmanAbstract:In response to an abundant fermentable carbon source and limiting nitrogen, diploid yeast cells differentiate to form pseudohyphae that consist of chains of elongated cells. The G-protein coupled receptor Gpr1 senses extracellular glucose and signals via the coupled Gα subunit Gpa2. Gpa2 then stimulates cAMP production by adenylyl cyclase and activates the cAMP signaling pathway to promote pseudohyphal differentiation in diploid cells. Recently, the Kelch Repeat proteins Gpb1 and Gpb2 were identified as effectors and Gssubunit mimics for Gpa2. The Gpr1- Gpa2-Gpb1/2-cAMP signaling cascade also controls a related cellular differentiation process, involving invasive growth that occurs in haploid cells grown on rich medium. Multiple signaling pathways function coordinately with the cAMP signaling pathway to govern both diploid pseudohyphal differentiation and haploid invasive growth. In this chapter, we review the current state of knowledge about the signaling cascades that sense nutrients and effect these alternative developmental cell fates.
-
The Gα Protein Gpa2 Controls Yeast Differentiation by Interacting with Kelch Repeat Proteins that Mimic Gβ Subunits
Molecular Cell, 2002Co-Authors: Toshiaki Harashima, Joseph HeitmanAbstract:Abstract G protein coupled receptors (GPCR) sense diverse ligands and signal via heterotrimeric G proteins. The Saccharomyces cerevisiae GPCR Gpr1 senses glucose and controls filamentous growth via an unusual Gα protein, Gpa2, which lacks any known Gβγ subunits. Our genetic and biochemical studies identify Gpa2 interaction partners (Gpb1/2, Gpg1) and provide evidence that these proteins function as G protein subunit mimics and signaling effectors. Gpb1 and Gpb2 lack the seven WD-40 Repeats found in Gβ subunits and instead contain seven Kelch Repeats implicated in protein-protein interactions. Gβ subunits and the Kelch Repeat protein galactose oxidase fold into strikingly similar seven-bladed β propellers. Our studies demonstrate that Gpa2 signals in conjunction with Gβ structural mimics and that homologous G protein subunits or effectors may be conserved in multicellular eukaryotes.
Jianxia Zhang - One of the best experts on this subject based on the ideXlab platform.
-
overexpression of vpeifp1 a novel f box Kelch Repeat protein from wild chinese vitis pseudoreticulata confers higher tolerance to powdery mildew by inducing thioredoxin z proteolysis
Plant Science, 2017Co-Authors: Jie Wang, Wenkong Yao, Lei Wang, Weihuo Tong, Chen Wang, Rui Bao, Changyue Jiang, Yazhou Yang, Jianxia Zhang, Xiping WangAbstract:An F-box protein (VpEIFP1) induced by Erysiphe necator was isolated from Vitis pseudoreticulata, a wild Chinese grapevine species naturally resistant to powdery mildew (PM). It contains an F-box domain and two Kelch-Repeat motifs. Expression profiles indicate the VpEIFP1 is strongly induced at both transcriptional and translational levels by PM infection. A subcellular localisation assay showed that VpEIFP1 is predominantly located in the nucleus and cytoplasm. Overexpression of VpEIFP1 accelerated the accumulation of hydrogen peroxide (H2O2) and up-regulated the expressions of ICS2, NPR1 and PR1 involved in defence responses, resulting in suppression of PM germination and growth. As an F-box protein, VpEIFP1 interacts with thioredoxin z (VpTrxz) in the yeast-two-hybrid (Y2H) assay and in the bimolecular fluorescence complementation (BiFC) assay. Decreased amounts of VpTrxz protein in transgenic grapevine leaves overexpressing VpEIFP1 were restored by proteasome inhibitor MG132, implying that VpEIFP1 mediated VpTrxz for degradation through the SCFVpEIFP1 (Skp1-Cullin-F-box) E3 ubiquitin ligase complex. The RNA interference line of VpTrxz showed increased H2O2 accumulation following PM inoculation. We propose VpEIFP1 positively modulates the grapevine defence response to PM by inducing the degradation of VpTrxz via the ubiquitin/26S proteasome system.
-
Overexpression of VpEIFP1, a novel F-box/Kelch-Repeat protein from wild Chinese Vitis pseudoreticulata, confers higher tolerance to powdery mildew by inducing thioredoxin z proteolysis.
Plant Science, 2017Co-Authors: Jie Wang, Wenkong Yao, Lei Wang, Weihuo Tong, Chen Wang, Rui Bao, Changyue Jiang, Yazhou Yang, Jianxia ZhangAbstract:An F-box protein (VpEIFP1) induced by Erysiphe necator was isolated from Vitis pseudoreticulata, a wild Chinese grapevine species naturally resistant to powdery mildew (PM). It contains an F-box domain and two Kelch-Repeat motifs. Expression profiles indicate the VpEIFP1 is strongly induced at both transcriptional and translational levels by PM infection. A subcellular localisation assay showed that VpEIFP1 is predominantly located in the nucleus and cytoplasm. Overexpression of VpEIFP1 accelerated the accumulation of hydrogen peroxide (H2O2) and up-regulated the expressions of ICS2, NPR1 and PR1 involved in defence responses, resulting in suppression of PM germination and growth. As an F-box protein, VpEIFP1 interacts with thioredoxin z (VpTrxz) in the yeast-two-hybrid (Y2H) assay and in the bimolecular fluorescence complementation (BiFC) assay. Decreased amounts of VpTrxz protein in transgenic grapevine leaves overexpressing VpEIFP1 were restored by proteasome inhibitor MG132, implying that VpEIFP1 mediated VpTrxz for degradation through the SCFVpEIFP1 (Skp1-Cullin-F-box) E3 ubiquitin ligase complex. The RNA interference line of VpTrxz showed increased H2O2 accumulation following PM inoculation. We propose VpEIFP1 positively modulates the grapevine defence response to PM by inducing the degradation of VpTrxz via the ubiquitin/26S proteasome system.
Mark Hannink - One of the best experts on this subject based on the ideXlab platform.
-
Conserved solvent and side-chain interactions in the 1.35 Angstrom structure of the Kelch domain of Keap1.
Acta crystallographica. Section D Biological crystallography, 2005Co-Authors: Lesa J Beamer, Christopher A Bottoms, Mark HanninkAbstract:The Kelch Repeat is a common sequence motif in eukaryotic genomes and is approximately 50 amino acids in length. The structure of the Kelch domain of the human Keap1 protein has previously been determined at 1.85 Angstrom, showing that each Kelch Repeat forms one blade of a six-bladed beta-propeller. Here, use of 1.35 Angstrom SAD data for de novo structure determination of the Kelch domain and for refinement at atomic resolution is described. The high quality and resolution of the diffraction data and phase information allows a detailed analysis of the role of solvent in the structure of the Kelch Repeat. Ten structurally conserved water molecules are identified in each blade of the Kelch beta-propeller. These appear to play distinct structural roles that include lining the central channel of the propeller, interacting with residues in loops between strands of the blade and making contacts with conserved residues in the Kelch Repeat. Furthermore, we identify a conserved C-H...pi hydrogen bond between two key residues in the consensus Kelch Repeat. This analysis extends our understanding of the structural roles of conserved residues in the Kelch Repeat and highlights the potential role of solvent in maintaining the fold of this common eukaryotic structural motif.
-
Conserved solvent and side-chain interactions in the 1.35 Angstrom structure of the Kelch domain of Keap1.
Acta Crystallographica Section D Biological Crystallography, 2005Co-Authors: Lesa J Beamer, Christopher A Bottoms, Mark HanninkAbstract:The Kelch Repeat is a common sequence motif in eukaryotic genomes and is approximately 50 amino acids in length. The structure of the Kelch domain of the human Keap1 protein has previously been determined at 1.85 A, showing that each Kelch Repeat forms one blade of a six-bladed β-propeller. Here, use of 1.35 A SAD data for de novo structure determination of the Kelch domain and for refinement at atomic resolution is described. The high quality and resolution of the diffraction data and phase information allows a detailed analysis of the role of solvent in the structure of the Kelch Repeat. Ten structurally conserved water molecules are identified in each blade of the Kelch β-propeller. These appear to play distinct structural roles that include lining the central channel of the propeller, interacting with residues in loops between strands of the blade and making contacts with conserved residues in the Kelch Repeat. Furthermore, we identify a conserved C—H⋯π hydrogen bond between two key residues in the consensus Kelch Repeat. This analysis extends our understanding of the structural roles of conserved residues in the Kelch Repeat and highlights the potential role of solvent in maintaining the fold of this common eukaryotic structural motif.
-
crystal structure of the Kelch domain of human keap1
Journal of Biological Chemistry, 2004Co-Authors: Xuchu Li, Mark Hannink, Donna D Zhang, Lesa J BeamerAbstract:Abstract Keap1 is a substrate adaptor protein for an ubiquitin ligase complex that targets the Nrf2 transcription factor for degradation. Keap1 binds Nrf2 through its C-terminal Kelch domain, which contains six copies of the evolutionarily conserved Kelch Repeat sequence motif. The structure of the Kelch domain from human Keap1 has been determined by x-ray crystallography to a resolution of 1.85 A. The Kelch domain forms a 6-bladed β-propeller structure, with residues at the C terminus forming the first strand in the first blade. Key structural roles have been identified for the highly conserved glycine, tyrosine, and tryptophan residues that define the Kelch Repeat sequence motif. In addition, we show that substitution of a single amino acid located within a loop that extends out from the bottom of the β-propeller structure abolishes binding of Nrf2. The structure of the Kelch domain of Keap1 represents a high quality model for the superfamily of eukaryotic Kelch Repeat proteins and provides insight into how disease-causing mutations perturb the structural integrity of the Kelch domain.
-
Crystallization and initial crystallographic analysis of the Kelch domain from human Keap1.
Acta crystallographica. Section D Biological crystallography, 2004Co-Authors: Donna Zhang, Mark Hannink, Lesa J BeamerAbstract:The human Keap1 protein is a substrate adaptor for an E3 ubiquitin ligase complex that specifically targets the transcription factor Nrf2 for degradation. Keap1 functions as a sensor of oxidative stress, such that the inhibition of Keap1-dependent degradation of Nrf2 activates a genetic program that protects cells from reactive chemicals and maintains cellular redox homeostasis. Keap1 interacts with Nrf2 through its C-terminal Kelch-Repeat domain. Kelch-Repeat domains are found in a large number of proteins and are predicted to assemble into a beta-propeller structure. Only a single Kelch-Repeat domain, that from the fungal enzyme galactose oxidase, has had its structure determined. Here, the crystallization of the Kelch domain of human Keap1 protein by hanging-drop vapor diffusion is reported in space group P6(5)22. Crystals diffract to 1.85 A resolution under cryocooling conditions. A selenomethionine-substituted version of the Kelch domain has also been purified and crystallizes isomorphously with the native protein. Structure determination by MAD phasing is under way. The role of Keap1 in oxidative stress and cytoprevention suggests that the Kelch domain will be an attractive target for therapeutic drug design.
-
Crystallization and initial crystallographic analysis of the Kelch domain from human Keap1.
Acta Crystallographica Section D Biological Crystallography, 2004Co-Authors: Donna D Zhang, Mark Hannink, Lesa J BeamerAbstract:The human Keap1 protein is a substrate adaptor for an E3 ubiquitin ligase complex that specifically targets the transcription factor Nrf2 for degradation. Keap1 functions as a sensor of oxidative stress, such that the inhibition of Keap1-dependent degradation of Nrf2 activates a genetic program that protects cells from reactive chemicals and maintains cellular redox homeostasis. Keap1 interacts with Nrf2 through its C-terminal Kelch-Repeat domain. Kelch-Repeat domains are found in a large number of proteins and are predicted to assemble into a β-propeller structure. Only a single Kelch-Repeat domain, that from the fungal enzyme galactose oxidase, has had its structure determined. Here, the crystallization of the Kelch domain of human Keap1 protein by hanging-drop vapor diffusion is reported in space group P6522. Crystals diffract to 1.85 A resolution under cryocooling conditions. A selenomethionine-substituted version of the Kelch domain has also been purified and crystallizes isomorphously with the native protein. Structure determination by MAD phasing is under way. The role of Keap1 in oxidative stress and cytoprevention suggests that the Kelch domain will be an attractive target for therapeutic drug design.
Jie Wang - One of the best experts on this subject based on the ideXlab platform.
-
overexpression of vpeifp1 a novel f box Kelch Repeat protein from wild chinese vitis pseudoreticulata confers higher tolerance to powdery mildew by inducing thioredoxin z proteolysis
Plant Science, 2017Co-Authors: Jie Wang, Wenkong Yao, Lei Wang, Weihuo Tong, Chen Wang, Rui Bao, Changyue Jiang, Yazhou Yang, Jianxia Zhang, Xiping WangAbstract:An F-box protein (VpEIFP1) induced by Erysiphe necator was isolated from Vitis pseudoreticulata, a wild Chinese grapevine species naturally resistant to powdery mildew (PM). It contains an F-box domain and two Kelch-Repeat motifs. Expression profiles indicate the VpEIFP1 is strongly induced at both transcriptional and translational levels by PM infection. A subcellular localisation assay showed that VpEIFP1 is predominantly located in the nucleus and cytoplasm. Overexpression of VpEIFP1 accelerated the accumulation of hydrogen peroxide (H2O2) and up-regulated the expressions of ICS2, NPR1 and PR1 involved in defence responses, resulting in suppression of PM germination and growth. As an F-box protein, VpEIFP1 interacts with thioredoxin z (VpTrxz) in the yeast-two-hybrid (Y2H) assay and in the bimolecular fluorescence complementation (BiFC) assay. Decreased amounts of VpTrxz protein in transgenic grapevine leaves overexpressing VpEIFP1 were restored by proteasome inhibitor MG132, implying that VpEIFP1 mediated VpTrxz for degradation through the SCFVpEIFP1 (Skp1-Cullin-F-box) E3 ubiquitin ligase complex. The RNA interference line of VpTrxz showed increased H2O2 accumulation following PM inoculation. We propose VpEIFP1 positively modulates the grapevine defence response to PM by inducing the degradation of VpTrxz via the ubiquitin/26S proteasome system.
-
Overexpression of VpEIFP1, a novel F-box/Kelch-Repeat protein from wild Chinese Vitis pseudoreticulata, confers higher tolerance to powdery mildew by inducing thioredoxin z proteolysis.
Plant Science, 2017Co-Authors: Jie Wang, Wenkong Yao, Lei Wang, Weihuo Tong, Chen Wang, Rui Bao, Changyue Jiang, Yazhou Yang, Jianxia ZhangAbstract:An F-box protein (VpEIFP1) induced by Erysiphe necator was isolated from Vitis pseudoreticulata, a wild Chinese grapevine species naturally resistant to powdery mildew (PM). It contains an F-box domain and two Kelch-Repeat motifs. Expression profiles indicate the VpEIFP1 is strongly induced at both transcriptional and translational levels by PM infection. A subcellular localisation assay showed that VpEIFP1 is predominantly located in the nucleus and cytoplasm. Overexpression of VpEIFP1 accelerated the accumulation of hydrogen peroxide (H2O2) and up-regulated the expressions of ICS2, NPR1 and PR1 involved in defence responses, resulting in suppression of PM germination and growth. As an F-box protein, VpEIFP1 interacts with thioredoxin z (VpTrxz) in the yeast-two-hybrid (Y2H) assay and in the bimolecular fluorescence complementation (BiFC) assay. Decreased amounts of VpTrxz protein in transgenic grapevine leaves overexpressing VpEIFP1 were restored by proteasome inhibitor MG132, implying that VpEIFP1 mediated VpTrxz for degradation through the SCFVpEIFP1 (Skp1-Cullin-F-box) E3 ubiquitin ligase complex. The RNA interference line of VpTrxz showed increased H2O2 accumulation following PM inoculation. We propose VpEIFP1 positively modulates the grapevine defence response to PM by inducing the degradation of VpTrxz via the ubiquitin/26S proteasome system.