The Experts below are selected from a list of 55053 Experts worldwide ranked by ideXlab platform
Kenneth H Fischbeck - One of the best experts on this subject based on the ideXlab platform.
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splice mutation in the iron sulfur cluster Scaffold Protein iscu causes myopathy with exercise intolerance
American Journal of Human Genetics, 2008Co-Authors: Fanny Mochel, Melanie A Knight, Wing Hang Tong, Dena G Hernandez, Karen Ayyad, Tanja Taivassalo, Peter M Andersen, Andrew B Singleton, Tracey A Rouault, Kenneth H FischbeckAbstract:A myopathy with severe exercise intolerance and myoglobinuria has been described in patients from northern Sweden, with associated deficiencies of succinate dehydrogenase and aconitase in skeletal muscle. We identified the gene for the iron-sulfur cluster Scaffold Protein ISCU as a candidate within a region of shared homozygosity among patients with this disease. We found a single mutation in ISCU that likely strengthens a weak splice acceptor site, with consequent exon retention. A marked reduction of ISCU mRNA and mitochondrial ISCU Protein in patient muscle was associated with a decrease in the iron regulatory Protein IRP1 and intracellular iron overload in skeletal muscle, consistent with a muscle-specific alteration of iron homeostasis in this disease. ISCU interacts with the Friedreich ataxia gene product frataxin in iron-sulfur cluster biosynthesis. Our results therefore extend the range of known human diseases that are caused by defects in iron-sulfur cluster biogenesis.
Hemayet Ullah - One of the best experts on this subject based on the ideXlab platform.
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Arabidopsis Scaffold Protein RACK1A interacts with diverse environmental stress and photosynthesis related Proteins
Plant signaling & behavior, 2013Co-Authors: Nabanita Kundu, Uvetta Dozier, Laurent Deslandes, Imre E. Somssich, Hemayet UllahAbstract:Scaffold Proteins are known to regulate important cellular processes by interacting with multiple Proteins to modulate molecular responses. RACK1 (Receptor for Activated C Kinase 1) is a WD-40 type Scaffold Protein, conserved in eukaryotes, from Chlamydymonas to plants and humans, expresses ubiquitously and plays regulatory roles in diverse signal transduction and stress response pathways. Here we present the use of Arabidopsis RACK1A, the predominant isoform of a 3-member family, as a bait to screen a split-ubiquitin based cDNA library. In total 97 Proteins from dehydration, salt stress, ribosomal and photosynthesis pathways are found to potentially interact with RACK1A. False positive interactions were eliminated following extensive selection based growth potentials. Confirmation of a sub-set of selected interactions is demonstrated through the co-transformation with individual plasmid containing cDNA and the respective bait. Interaction of diverse Proteins points to a regulatory role of RACK1A in the c...
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Arabidopsis Scaffold Protein RACK1A interacts with diverse environmental stress and photosynthesis related Proteins.
Plant Signaling and Behavior, 2013Co-Authors: Nabanita Kundu, Uvetta Dozier, Laurent Deslandes, Imre E. Somssich, Hemayet UllahAbstract:Scaffold Proteins are known to regulate important cellular processes by interacting with multiple Proteins to modulate molecular responses. RACK1 (Receptor for Activated C Kinase 1) is a WD-40 type Scaffold Protein, conserved in eukaryotes, from Chlamydymonas to plants and humans, expresses ubiquitously and plays regulatory roles in diverse signal transduction and stress response pathways. Here we present the use of Arabidopsis RACK1A, the predominant isoform of a 3-member family, as a bait to screen a split-ubiquitin based cDNA library. In total 97 Proteins from dehydration, salt stress, ribosomal and photosynthesis pathways are found to potentially interact with RACK1A. False positive interactions were eliminated following extensive selection based growth potentials. Confirmation of a sub-set of selected interactions is demonstrated through the co-transformation with individual plasmid containing cDNA and the respective bait. Interaction of diverse Proteins points to a regulatory role of RACK1A in the cross-talk between signaling pathways. Promoter analysis of the stress and photosynthetic pathway genes revealed conserved transcription factor binding sites. RACK1A is known to be a multifunctional Protein and the current identification of potential interacting Proteins and future in vivo elucidations of the physiological basis of such interactions will shed light on the possible molecular mechanisms that RACK1A uses to regulate diverse signaling pathways.
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arabidopsis Scaffold Protein rack1a modulates rare sugar d allose regulated gibberellin signaling
Plant Signaling & Behavior, 2012Co-Authors: Herman Fennell, Abdulquadri Olawin, Rahman Md Mizanur, Jingui Chen, Ken Izumori, Hemayet UllahAbstract:As energy sources and structural components, sugars are the central regulators of plant growth and development. In addition to the abundant natural sugars in plants, more than 50 different kinds of rare sugars exist in nature, several of which show distinct roles in plant growth and development. Recently, one of the rare sugars, D-allose, an epimer of D-glucose at C3, is found to suppress plant hormone gibberellin (GA) signaling in rice. Scaffold Protein RACK1A in the model plant Arabidopsis is implicated in the GA pathway as rack1a knockout mutants show insensitivity to GA in GA-induced seed germination. Using genetic knockout lines and a reporter gene, the functional role of RACK1A in the D-allose pathway was investigated. It was found that the rack1a knockout seeds showed hypersensitivity to D-allose-induced inhibition of seed germination, implicating a role for RACK1A in the D-allose mediated suppression of seed germination. On the other hand, a functional RACK1A in the background of the double knocko...
Jeverson Frazzon - One of the best experts on this subject based on the ideXlab platform.
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enterococcus faecalis sufu Scaffold Protein enhances sufs desulfurase activity by acquiring sulfur from its cysteine 153
Biochimica et Biophysica Acta, 2011Co-Authors: Gustavo Pelicioli Riboldi, Jaim S Oliveira, Jeverson FrazzonAbstract:Iron-sulfur [Fe-S] clusters are inorganic prosthetic groups that play essential roles in all living organisms. In vivo [Fe-S] cluster biogenesis requires enzymes involved in iron and sulfur mobilization, assembly of clusters, and delivery to their final acceptor. In these systems, a cysteine desulfurase is responsible for the release of sulfide ions, which are incorporated into a Scaffold Protein for subsequent [Fe-S] cluster assembly. Although three machineries have been shown to be present in Proteobacteria for [Fe-S] cluster biogenesis (NIF, ISC, and SUF), only the SUF machinery has been found in Firmicutes. We have recently described the structural similarities and differences between Enterococcus faecalis and Escherichia coli SufU Proteins, which prompted the proposal that SufU is the Scaffold Protein of the E. faecalis sufCDSUB system. The present work aims at elucidating the biological roles of E. faecalis SufS and SufU Proteins in [Fe-S] cluster assembly. We show that SufS has cysteine desulfurase activity and cysteine-365 plays an essential role in catalysis. SufS requires SufU as activator to [4Fe-4S] cluster assembly, as its ortholog, IscU, in which the conserved cysteine-153 acts as a proximal sulfur acceptor for transpersulfurization reaction.
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chloroplast hcf101 is a Scaffold Protein for 4fe 4s cluster assembly
Biochemical Journal, 2010Co-Authors: Serena Schwenkert, Jeverson Frazzon, Daili J.a. Netz, Antonio J Pierik, Eckhard Bill, Jeferson Gross, Roland Lill, Jörg MeurerAbstract:Oxygen-evolving chloroplasts possess their own iron-sulfur cluster assembly Proteins including members of the SUF (sulfur mobilization) and the NFU family. Recently, the chloroplast Protein HCF101 (high chlorophyll fluorescence 101) has been shown to be essential for the accumulation of the membrane complex Photosystem I and the soluble ferredoxin-thioredoxin reductases, both containing [4Fe-4S] clusters. The Protein belongs to the FSC-NTPase ([4Fe-4S]-cluster-containing P-loop NTPase) superfamily, several members of which play a crucial role in Fe/S cluster biosynthesis. Although the C-terminal ISC-binding site, conserved in other members of the FSC-NTPase family, is not present in chloroplast HCF101 homologues using Mossbauer and EPR spectroscopy, we provide evidence that HCF101 binds a [4Fe-4S] cluster. 55Fe incorporation studies of mitochondrially targeted HCF101 in Saccharomyces cerevisiae confirmed the assembly of an Fe/S cluster in HCF101 in an Nfs1-dependent manner. Site-directed mutagenesis identified three HCF101-specific cysteine residues required for assembly and/or stability of the cluster. We further demonstrate that the reconstituted cluster is transiently bound and can be transferred from HCF101 to a [4Fe-4S] apoProtein. Together, our findings suggest that HCF101 may serve as a chloroplast Scaffold Protein that specifically assembles [4Fe-4S] clusters and transfers them to the chloroplast membrane and soluble target Proteins.
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Chloroplast HCF101 is a Scaffold Protein for [4Fe-4S] cluster assembly
Biochemical Journal, 2009Co-Authors: Serena Schwenkert, Jeverson Frazzon, Daili J.a. Netz, Antonio J Pierik, Eckhard Bill, Jeferson Gross, Roland Lill, Jörg MeurerAbstract:Oxygen evolving chloroplasts possess their own iron-sulfur cluster assembly Proteins including members of the SUF and the NFU family. Recently, the chloroplast Protein HCF101 (high chlorophyll fluorescence) has been shown to be essential for the accumulation of the membrane complex photosystem I and the soluble ferredoxin-thioredoxin reductases, both containing [4Fe-4S] clusters. The Protein belongs to the FSC ([4Fe-4S]-cluster) superfamily of P-loop NTPases, several members of which play a crucial role in Fe/S cluster biosynthesis. Although the C-terminal Fe/S cluster binding site conserved in other members of the FSC family is not present in chloroplast HCF101 homologues, using Mössbauer and EPR spectroscopy, we provide evidence that HCF101 binds a [4Fe-4S] cluster. 55Fe incorporation studies of mitochondria-targeted HCF101 in S. cerevisiae confirmed the assembly of an Fe/S cluster in HCF101 in a Nfs1-dependent manner. Site-directed mutagenesis identified three HCF101-specific cysteine residues required for assembly and/or stability of the cluster. We further demonstrate that the reconstituted cluster is transiently bound and can be transferred from HCF101 to a [4Fe-4S] apoProtein. Together, our findings suggest that HCF101 may serve as a chloroplast Scaffold Protein that specifically assembles [4Fe-4S] clusters and transfers them to chloroplast membrane and soluble target Proteins.
Mark E. Bowen - One of the best experts on this subject based on the ideXlab platform.
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Mapping the Conformational Dynamics of the Scaffold Protein PSD-95
Biophysical Journal, 2015Co-Authors: Claus A.m. Seidel, Jakub Kubiak, Suren Felekyan, Daniel Rohrbeck, James J. Mccann, Mark E. BowenAbstract:Scaffold Proteins form a dynamic framework to organize signal transduction by conjoining modular Protein-binding domains. Scaffolds contain folded domains that are well understood but also disordered regions, which provide a challenge to structural biology. The folded domain structures for the Scaffold Protein PSD-95 were long known but such fragmentary knowledge lacks methods to assemble these pieces. We used single-molecule FRET studies with multi-parameter fluorescence detection [1] and filtered fluorescence correlation spectroscopy [2, 3] to describe the native state ensemble of this canonical Scaffold Protein.
Fanny Mochel - One of the best experts on this subject based on the ideXlab platform.
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splice mutation in the iron sulfur cluster Scaffold Protein iscu causes myopathy with exercise intolerance
American Journal of Human Genetics, 2008Co-Authors: Fanny Mochel, Melanie A Knight, Wing Hang Tong, Dena G Hernandez, Karen Ayyad, Tanja Taivassalo, Peter M Andersen, Andrew B Singleton, Tracey A Rouault, Kenneth H FischbeckAbstract:A myopathy with severe exercise intolerance and myoglobinuria has been described in patients from northern Sweden, with associated deficiencies of succinate dehydrogenase and aconitase in skeletal muscle. We identified the gene for the iron-sulfur cluster Scaffold Protein ISCU as a candidate within a region of shared homozygosity among patients with this disease. We found a single mutation in ISCU that likely strengthens a weak splice acceptor site, with consequent exon retention. A marked reduction of ISCU mRNA and mitochondrial ISCU Protein in patient muscle was associated with a decrease in the iron regulatory Protein IRP1 and intracellular iron overload in skeletal muscle, consistent with a muscle-specific alteration of iron homeostasis in this disease. ISCU interacts with the Friedreich ataxia gene product frataxin in iron-sulfur cluster biosynthesis. Our results therefore extend the range of known human diseases that are caused by defects in iron-sulfur cluster biogenesis.
