The Experts below are selected from a list of 190536 Experts worldwide ranked by ideXlab platform
Roland Lill - One of the best experts on this subject based on the ideXlab platform.
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the role of mitochondria in cytosolic nuclear iron sulfur Protein biogenesis and in cellular iron regulation
Current Opinion in Microbiology, 2014Co-Authors: Roland Lill, Vasundara Srinivasan, Ulrich MühlenhoffAbstract:Mitochondria are indispensable in eukaryotes because of their function in the maturation of cytosolic and nuclear iron–sulfur Proteins that are essential for DNA synthesis and repair, tRNA modification, and Protein translation. The mitochondrial Fe/S cluster Assembly machinery not only generates the organelle's iron–sulfur Proteins, but also extra-mitochondrial ones. Biogenesis of the latter Proteins requires the mitochondrial ABC transporter Atm1 that exports a sulfur-containing compound in a glutathione-dependent fashion. The process is further assisted by the cytosolic iron–sulfur Protein Assembly machinery. Here, we discuss the knowns and unknowns of the mitochondrial export process that is also crucial for signaling the cellular iron status to the regulatory systems involved in the maintenance of cellular iron homeostasis.
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Human Nbp35 is essential for both cytosolic iron-sulfur Protein Assembly and iron homeostasis.
Molecular and Cellular Biology, 2008Co-Authors: Oliver Stehling, Antonio J Pierik, Daili Netz, Brigitte Niggemeyer, Ralf Rösser, Richard Eisenstein, Helene Puccio, Roland LillAbstract:The maturation of cytosolic iron-sulfur (Fe/S) Proteins in mammalian cells requires components of the mitochondrial iron-sulfur cluster Assembly and export machineries. Little is known about the cytosolic components that may facilitate the Assembly process. Here, we identified the cytosolic soluble P-loop NTPase termed huNbp35 (also known as Nubp1) as an Fe/S Protein, and we defined its role in the maturation of Fe/S Proteins in HeLa cells. Depletion of huNbp35 by RNA interference decreased cell growth considerably, indicating its essential function. The deficiency in huNbp35 was associated with an impaired maturation of the cytosolic Fe/S Proteins glutamine phosphoribosylpyrophosphate amidotransferase and iron regulatory Protein 1 (IRP1), while mitochondrial Fe/S Proteins remained intact. Consequently, huNbp35 is specifically involved in the formation of extramitochondrial Fe/S Proteins. The impaired maturation of IRP1 upon huNbp35 depletion had profound consequences for cellular iron metabolism, leading to decreased cellular H-ferritin, increased transferrin receptor levels, and higher transferrin uptake. These properties clearly distinguished huNbp35 from its yeast counterpart Nbp35, which is essential for cytosolic-nuclear Fe/S Protein Assembly but plays no role in iron regulation. huNbp35 formed a complex with its close homologue huCfd1 (also known as Nubp2) in vivo, suggesting the existence of a heteromeric P-loop NTPase complex that is required for both cytosolic Fe/S Protein Assembly and cellular iron homeostasis.
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the cfd1 nbp35 complex acts as a scaffold for iron sulfur Protein Assembly in the yeast cytosol
Nature Chemical Biology, 2007Co-Authors: Daili J A Netz, Ulrich Mühlenhoff, Antonio J Pierik, Martin Stumpfig, Roland LillAbstract:The Cfd1–Nbp35 complex acts as a scaffold for iron-sulfur Protein Assembly in the yeast cytosol
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The Cfd1–Nbp35 complex acts as a scaffold for iron-sulfur Protein Assembly in the yeast cytosol
Nature chemical biology, 2007Co-Authors: Daili J A Netz, Ulrich Mühlenhoff, Antonio J Pierik, Martin Stumpfig, Roland LillAbstract:Biogenesis of iron-sulfur ([Fe-S]) Proteins in eukaryotes requires the function of complex Proteinaceous machineries in both mitochondria and cytosol. In contrast to the mitochondrial pathway, little is known about [Fe-S] Protein Assembly in the cytosol. So far, four highly conserved Proteins (Cfd1, Nbp35, Nar1 and Cia1) have been identified as members of the cytosolic [Fe-S] Protein Assembly machinery, but their molecular function is unresolved. Using in vivo and in vitro approaches, we found that the soluble P-loop NTPases Cfd1 and Nbp35 form a complex and bind up to three [4Fe-4S] clusters, one at the N terminus of Nbp35 and one each at a new C-terminal cysteine-rich motif present in both Proteins. These labile [Fe-S] clusters can be rapidly transferred and incorporated into target [Fe-S] apoProteins in a Nar1- and Cia1-dependent fashion. Our data suggest that the Cfd1-Nbp35 complex functions as a novel scaffold for [Fe-S] cluster Assembly in the eukaryotic cytosol.
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mechanisms of iron sulfur Protein maturation in mitochondria cytosol and nucleus of eukaryotes
Biochimica et Biophysica Acta, 2006Co-Authors: Roland Lill, Daili J A Netz, Antonio J Pierik, Anja Hausmann, Rafal Dutkiewicz, Hanspeter Elsasser, Oliver Stehling, Eugen I Urzica, Ulrich MühlenhoffAbstract:Iron–sulfur (Fe/S) clusters are important cofactors of numerous Proteins involved in electron transfer, metabolic and regulatory processes. In eukaryotic cells, known Fe/S Proteins are located within mitochondria, the nucleus and the cytosol. Over the past years the molecular basis of Fe/S cluster synthesis and incorporation into apoProteins in a living cell has started to become elucidated. Biogenesis of these simple inorganic cofactors is surprisingly complex and, in eukaryotes such as Saccharomyces cerevisiae, is accomplished by three distinct Proteinaceous machineries. The ‘iron–sulfur cluster (ISC) Assembly machinery’ of mitochondria was inherited from the bacterial ancestor of mitochondria. ISC components are conserved in eukaryotes from yeast to man. The key principle of biosynthesis is the Assembly of the Fe/S cluster on a scaffold Protein before it is transferred to target apoProteins. Cytosolic and nuclear Fe/S Protein maturation also requires the function of the mitochondrial ISC Assembly system. It is believed that mitochondria contribute a still unknown compound to biogenesis outside the organelle. This compound is exported by the mitochondrial ‘ISC export machinery’ and utilised by the ‘cytosolic iron–sulfur Protein Assembly (CIA) machinery’. Components of these two latter systems are also highly conserved in eukaryotes. Defects in the mitochondrial ISC Assembly and export systems, but not in the CIA machinery have a strong impact on cellular iron uptake and intracellular iron distribution showing that mitochondria are crucial for both cellular Fe/S Protein Assembly and iron homeostasis.
Ulrich Mühlenhoff - One of the best experts on this subject based on the ideXlab platform.
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the role of mitochondria in cytosolic nuclear iron sulfur Protein biogenesis and in cellular iron regulation
Current Opinion in Microbiology, 2014Co-Authors: Roland Lill, Vasundara Srinivasan, Ulrich MühlenhoffAbstract:Mitochondria are indispensable in eukaryotes because of their function in the maturation of cytosolic and nuclear iron–sulfur Proteins that are essential for DNA synthesis and repair, tRNA modification, and Protein translation. The mitochondrial Fe/S cluster Assembly machinery not only generates the organelle's iron–sulfur Proteins, but also extra-mitochondrial ones. Biogenesis of the latter Proteins requires the mitochondrial ABC transporter Atm1 that exports a sulfur-containing compound in a glutathione-dependent fashion. The process is further assisted by the cytosolic iron–sulfur Protein Assembly machinery. Here, we discuss the knowns and unknowns of the mitochondrial export process that is also crucial for signaling the cellular iron status to the regulatory systems involved in the maintenance of cellular iron homeostasis.
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the cfd1 nbp35 complex acts as a scaffold for iron sulfur Protein Assembly in the yeast cytosol
Nature Chemical Biology, 2007Co-Authors: Daili J A Netz, Ulrich Mühlenhoff, Antonio J Pierik, Martin Stumpfig, Roland LillAbstract:The Cfd1–Nbp35 complex acts as a scaffold for iron-sulfur Protein Assembly in the yeast cytosol
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The Cfd1–Nbp35 complex acts as a scaffold for iron-sulfur Protein Assembly in the yeast cytosol
Nature chemical biology, 2007Co-Authors: Daili J A Netz, Ulrich Mühlenhoff, Antonio J Pierik, Martin Stumpfig, Roland LillAbstract:Biogenesis of iron-sulfur ([Fe-S]) Proteins in eukaryotes requires the function of complex Proteinaceous machineries in both mitochondria and cytosol. In contrast to the mitochondrial pathway, little is known about [Fe-S] Protein Assembly in the cytosol. So far, four highly conserved Proteins (Cfd1, Nbp35, Nar1 and Cia1) have been identified as members of the cytosolic [Fe-S] Protein Assembly machinery, but their molecular function is unresolved. Using in vivo and in vitro approaches, we found that the soluble P-loop NTPases Cfd1 and Nbp35 form a complex and bind up to three [4Fe-4S] clusters, one at the N terminus of Nbp35 and one each at a new C-terminal cysteine-rich motif present in both Proteins. These labile [Fe-S] clusters can be rapidly transferred and incorporated into target [Fe-S] apoProteins in a Nar1- and Cia1-dependent fashion. Our data suggest that the Cfd1-Nbp35 complex functions as a novel scaffold for [Fe-S] cluster Assembly in the eukaryotic cytosol.
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mechanisms of iron sulfur Protein maturation in mitochondria cytosol and nucleus of eukaryotes
Biochimica et Biophysica Acta, 2006Co-Authors: Roland Lill, Daili J A Netz, Antonio J Pierik, Anja Hausmann, Rafal Dutkiewicz, Hanspeter Elsasser, Oliver Stehling, Eugen I Urzica, Ulrich MühlenhoffAbstract:Iron–sulfur (Fe/S) clusters are important cofactors of numerous Proteins involved in electron transfer, metabolic and regulatory processes. In eukaryotic cells, known Fe/S Proteins are located within mitochondria, the nucleus and the cytosol. Over the past years the molecular basis of Fe/S cluster synthesis and incorporation into apoProteins in a living cell has started to become elucidated. Biogenesis of these simple inorganic cofactors is surprisingly complex and, in eukaryotes such as Saccharomyces cerevisiae, is accomplished by three distinct Proteinaceous machineries. The ‘iron–sulfur cluster (ISC) Assembly machinery’ of mitochondria was inherited from the bacterial ancestor of mitochondria. ISC components are conserved in eukaryotes from yeast to man. The key principle of biosynthesis is the Assembly of the Fe/S cluster on a scaffold Protein before it is transferred to target apoProteins. Cytosolic and nuclear Fe/S Protein maturation also requires the function of the mitochondrial ISC Assembly system. It is believed that mitochondria contribute a still unknown compound to biogenesis outside the organelle. This compound is exported by the mitochondrial ‘ISC export machinery’ and utilised by the ‘cytosolic iron–sulfur Protein Assembly (CIA) machinery’. Components of these two latter systems are also highly conserved in eukaryotes. Defects in the mitochondrial ISC Assembly and export systems, but not in the CIA machinery have a strong impact on cellular iron uptake and intracellular iron distribution showing that mitochondria are crucial for both cellular Fe/S Protein Assembly and iron homeostasis.
Karen H. Ashe - One of the best experts on this subject based on the ideXlab platform.
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A specific amyloid-|[beta]| Protein Assembly in the brain impairs memory
Nature, 2006Co-Authors: Sylvain Lesné, Ming Teng Koh, Linda Kotilinek, Rakez Kayed, Charles G. Glabe, Austin J. Yang, Michela Gallagher, Karen H. AsheAbstract:Memory function often declines with age, and is believed to deteriorate initially because of changes in synaptic function rather than loss of neurons. Some individuals then go on to develop Alzheimer's disease with neurodegeneration. Here we use Tg2576 mice, which express a human amyloid-beta precursor Protein (APP) variant linked to Alzheimer's disease, to investigate the cause of memory decline in the absence of neurodegeneration or amyloid-beta Protein amyloidosis. Young Tg2576 mice ( 14 months old) form abundant neuritic plaques containing amyloid-beta (refs 3-6). We found that memory deficits in middle-aged Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-beta Assembly, which we term Abeta*56 (Abeta star 56). Abeta*56 purified from the brains of impaired Tg2576 mice disrupts memory when administered to young rats. We propose that Abeta*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease.
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a specific amyloid beta Protein Assembly in the brain impairs memory
Nature, 2006Co-Authors: Sylvain Lesné, Ming Teng Koh, Linda Kotilinek, Rakez Kayed, Charles G. Glabe, Austin J. Yang, Michela Gallagher, Karen H. AsheAbstract:Memory function often declines with age, and is believed to deteriorate initially because of changes in synaptic function rather than loss of neurons. Some individuals then go on to develop Alzheimer's disease with neurodegeneration. Here we use Tg2576 mice, which express a human amyloid-beta precursor Protein (APP) variant linked to Alzheimer's disease, to investigate the cause of memory decline in the absence of neurodegeneration or amyloid-beta Protein amyloidosis. Young Tg2576 mice ( 14 months old) form abundant neuritic plaques containing amyloid-beta (refs 3-6). We found that memory deficits in middle-aged Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-beta Assembly, which we term Abeta*56 (Abeta star 56). Abeta*56 purified from the brains of impaired Tg2576 mice disrupts memory when administered to young rats. We propose that Abeta*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease.
Nancy R. Forde - One of the best experts on this subject based on the ideXlab platform.
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Optical tweezers approaches for probing multiscale Protein mechanics and Assembly
Frontiers in Molecular Biosciences, 2020Co-Authors: Kathrin Lehmann, Marjan Shayegan, Gerhard A. Blab, Nancy R. FordeAbstract:Multi-step Assembly of individual Protein building blocks is key to the formation of essential higher-order structures inside and outside of cells. Optical tweezers is a technique well suited to investigate the mechanics and dynamics of these structures at a variety of size scales. In this mini-review, we highlight experiments that have used optical tweezers to investigate Protein Assembly and mechanics, with a focus on the extracellular matrix Protein collagen. These examples demonstrate how optical tweezers can be used to study mechanics across length scales, ranging from the single-molecule level to fibrils to Protein networks. We discuss challenges in experimental design and interpretation, opportunities for integration with other experimental modalities, and applications of optical tweezers to current questions in Protein mechanics and Assembly.
Luc Brunsveld - One of the best experts on this subject based on the ideXlab platform.
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Designed Asymmetric Protein Assembly on a Symmetric Scaffold.
Angewandte Chemie (International ed. in English), 2020Co-Authors: Lenne J. M. Lemmens, Job A.l. Roodhuizen, Tom F. A. De Greef, Albert J. Markvoort, Luc BrunsveldAbstract:Cellular signaling is regulated by the Assembly of Proteins into higher-order complexes. Bottom-up creation of synthetic Protein assemblies, especially asymmetric complexes, is highly challenging. Presented here is the design and implementation of asymmetric Assembly of a ternary Protein complex facilitated by Rosetta modeling and thermodynamic analysis. The wild-type symmetric CT32-CT32 interface of the 14-3-3-CT32 complex was targeted, ultimately favoring asymmetric Assembly on the 14-3-3 scaffold. Biochemical studies, supported by mass-balance models, allowed characterization of the parameters driving asymmetric Assembly. Importantly, our work reveals that both the individual binding affinities and cooperativity between the assembling components are crucial when designing higher-order Protein complexes. Enzyme complementation on the 14-3-3 scaffold highlighted that interface engineering of a symmetric ternary complex generates asymmetric Protein complexes with new functions.
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Cucurbit[8]uril templated supramolecular ring structure formation and Protein Assembly modulation
Chemical Communications, 2015Co-Authors: M Mellany Ramaekers, Spw Sjors Wijnands, Luc Brunsveld, Jacques J.m. Van Dongen, Pyw Patricia DankersAbstract:The interplay of Phe-Gly-Gly (FGG)-tagged Proteins and bivalent FGG-tagged penta(ethylene glycol) as guest molecules with cucurbit[8]uril (Q8) hosts is studied to modulate the supramolecular Assembly process. Ring structure formation of the bivalent guest molecule with Q8 leads to enhanced binding properties and efficient inhibition of Protein assemblies.
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Dynamic and bio-orthogonal Protein Assembly along a supramolecular polymer
Chemical Science, 2013Co-Authors: Katja Petkau-milroy, Da Dana Uhlenheuer, A. J. H. Spiering, Jef A. J. M. Vekemans, Luc BrunsveldAbstract:Dynamic Protein Assembly along supramolecular columnar polymers has been achieved through the site-specific covalent attachment of different SNAP-tag fusion Proteins to self-assembled benzylguanine-decorated discotics. The self-Assembly of monovalent discotics into supramolecular polymers creates a multivalent, bio-orthogonal and self-regulating framework for Protein Assembly. The intrinsic reversibility of supramolecular interactions results in reorganization and exchange of building blocks allowing for dynamic intermixing of Protein-functionalized discotics between different self-assembled polymers, leading to self-optimization of Protein arrangement and distance as evidenced by efficient energy transfer between fluorescent Proteins.
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Protein Assembly along a supramolecular wire
Chemical communications (Cambridge England), 2010Co-Authors: Marion K. Müller, Katja Petkau, Luc BrunsveldAbstract:Discotic molecules self-assemble into supramolecular wires that act as platforms for directed Protein Assembly via appended biotin functionalities.
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A synthetic supramolecular construct modulating Protein Assembly in cells
Angewandte Chemie (International ed. in English), 2007Co-Authors: Li Zhang, Luc BrunsveldAbstract:Supramolecular chemistry in the cell: Synthetic supramolecular constructs ligated to Proteins modulate Protein Assembly (see picture). The interaction between the supramolecular elements is operative both in vitro and in cells, and drives the Proteins to assemble, as revealed by a strong FRET effect between the engineered Proteins.
