Post-translational Modifications of Eukaryotic Protein Synthesis Elongation Factor-2 PDF Download
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Author: Bent Riis
Publisher:
ISBN: 9789171532534
Category :
Languages : en
Pages : 51
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Book Description
Author: Bent Riis
Publisher:
ISBN: 9789171532534
Category :
Languages : en
Pages : 51
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Book Description
Author: Lon Dinh Phan
Publisher:
ISBN:
Category : Genetic translation
Languages : en
Pages : 238
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Book Description
Author: Sarah Anne Veldman
Publisher:
ISBN:
Category : Genetic translation
Languages : en
Pages : 310
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Author: Yugang Zhang
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Diphthamide is a unique post-translational modification on eukaryotic and archaeal elongation factor 2 (eEF2). Like diphthamide, hypusine is a unique post-translational modification on eukaryotic initiation factor 5a (eIF5A). These modifications were identified decades ago. Deletion of these modifications in animal model cause severe developmental defects. However, the biosynthesis and biological function of the modifications are not fully understood.The biosynthesis of diphthamide involves 4 steps and at least 7 proteins. The first step biosynthesis of diphthamide in Saccharomyces cerevisiae requires a unique radical SAM complex, Dph1-Dph2. The function of Dph1-Dph2 requires an oxygen-sensitive [4Fe-4S] cluster. However, the cluster is easily degraded into [3Fe-4S] in cytosol. We found that the small iron containing protein Dph3 can provide additional Fe during the reaction. The Dph1-Dph2-Dph3 is the first radical SAM enzyme system to maintain activity in the presence of oxygen. Dph3-like protein is likely to present to help other radical SAM enzymes to keep activity in the cytosol. The biological function of diphthamide was not understood. Diphthamide was proposed to suppress -1 frameshift in translation. Through genome wide profiling for potential -1 frameshift site, we identified that TORC1/mTORC1 signaling pathway is affected by the deletion of diphthamide. Diphthamide deletion suppresses translation of TORC1 activating proteins. Our results suggest diphthamide is essential for translating complex proteome and provide an explanation why diphthamide is evolutionary conserved and why diphthamide deletion can cause sever developmental defects. Deoxyhypusine hydroxylation is the second step biosynthesis of hypusine. The biological function of this step is not known. The enzymatic reaction for deoxyhypusine hydroxylation requires oxygen. We found that deletion of deoxyhypusine hydroxylase compromised yeast respiration through translation downregulation of protein involved in respiration. The translation suppression is through the N-terminal coding sequence. Deletion of the modification affects a set of N-terminal sequence translation and affects mitochondrial proteins, proteins essential in oxidative stress response and heat shock response. The discovery of the function of post-translation modification through scrutinizing substrate in biochemical reactions can be generalized. During the investigation of the function of diphthamide, we discovered that treatment of rapamycin can cause different regulations for isozymes that perform the same enzymatic function. Through enzymological and biochemical studies, we demonstrate that a rapamycin-upregulated enolase isozyme (Eno1) favors gluconeogenesis, and a rapamycin-upregulated alcohol dehydrogenase isozyme (Ald4) promotes the reduction of NAD+ to NADH. Gene deletion study in yeast showed that the Eno1 and Ald4 are important for yeast survival in less favorable growth conditions. Our study thus highlights the different metabolic needs of cells under different conditions and how nature chooses different isozymes to fit the metabolic needs. Furthermore, we discovered that the active site cysteine of Ald4 can form disulfide bond with the adjacent cysteine under oxidative stress. This response promotes yeast survival under oxidative stress.
Author: David Harold Giles
Publisher:
ISBN:
Category :
Languages : en
Pages : 202
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Book Description
Translation of mRNA to protein is essential to all life, and is carried out by the ribosome with the assistance of various initiation and elongation factors. The rate and location at which translation occurs is subject to regulation by an intricate network of positive and negative signaling mechanisms. Such regulation allows the cell to respond to changes in external conditions, such as a sudden drop in nutrient availability. In higher eukaryotes, a key component of this regulation is the phosphorylation of elongation factor 2 (eEF-2) - the enzyme which catalyzes ribosome translocation along the mRNA - by eEF-2 kinase (eEF-2K) on Thr56. This event impedes the affinity of eEF-2 for the ribosome and therefore lowers the rate of protein synthesis. The activity of eEF-2K is tightly regulated by upstream signals, including Ca2+-calmodulin and post-translational modification. Aberrant regulation of the eEF-2K axis is known in various disease states, including cancer and depression, yet the molecular mechanisms by which eEF-2K processes the multiple signals that communicate with it are poorly defined. This gap in knowledge precludes the rational design of eEF-2Ktargeting treatments which may be effective at treating such diseases. Here, three broad topics are discussed. First, an overview of what is currently known about the structure, function, and regulation of eEF-2K is presented. Second, we elucidate the mechanisms by which eEF-2K integrates signals at the nutrient-sensitive signaling node. Finally, we characterize a highly active form of eEF-2K which provides insight into the potential structure-function relationship of key portions of the enzyme. Taken together, this work is an important step towards a complete description of the biochemical mechanisms by which eEF-2K is regulated by diverse inputs
Author:
Publisher:
ISBN: 9780815332183
Category : Cells
Languages : en
Pages : 0
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Book Description
Author: Antonius M. VanDongen
Publisher: CRC Press
ISBN: 142004415X
Category : Medical
Languages : en
Pages : 368
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Book Description
The NMDA receptor plays a critical role in the development of the central nervous system and in adult neuroplasticity, learning, and memory. Therefore, it is not surprising that this receptor has been widely studied. However, despite the importance of rhythms for the sustenance of life, this aspect of NMDAR function remains poorly studied. Written
Author: Alan E. Smith
Publisher: Springer Science & Business Media
ISBN: 9400957432
Category : Science
Languages : en
Pages : 65
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Book Description
46 3. 2 mRNA metabolism 47 3. 3 Initiation complex formation 3. 3. 1 Binding of initiator tRNA 47 3. 3. 2 Binding of messenger RNA 50 3. 4 Elongation 56 3. 5 Termination of protein biosynthesis and post-translational modification 59 RNA phage protein synthesis 61 3. 6 References 63 Index 64 1 Introduction possible control processes operating to adjust 1. 1 The problem protein synthesis to the needs of the cells and The discovery that the genetic material of organism. It will be assumed that the reader has living organisms is DNA, and the later de some knowledge of molecular biology in gen monstration that the DNA molecule is a eral and protein biosynthesis in particular, but double helix were both great milestones in twentieth century science, and formed the by way of introduction each of the major molecules and stages of the process will be foundation of the new discipline of molecular described in simple terms, and in subsequent biology. But even after these momentous dis chapters each will be discussed again in coveries, the detailed mechanism by which such genetic material could be expressed as the struc greater depth. tural and catalytic proteins which play so im portant a role in the functioning of all living 1. 2 Overall steps in protein biosynthesis The information encoded in the two comple cells was still not obvious.
Author: J.M. Storey
Publisher: Elsevier
ISBN: 0080541070
Category : Science
Languages : en
Pages : 357
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Book Description
In this volume of Cell and Molecular Responses to Stress articles provide up-to-date information on key areas of signal sensing (sensing of pain, heat, cold, light, infrared radiation), molecules involved in the intracellular transmission of these signals, metabolic responses to stress including changes in gene expression and production of specialized proteins that aid cell responses to factors including interrupted blood supply (ischemia), oxygen limitation (hypoxia/anoxia), freezing and dehydration, amino acid limitation, radiation and processing drugs. There are chapters which also provide insights into new technologies (such as cDNA arrays), analysis of metabolic control theory (a key method for analysing stress effects on cells), and examine how enzymes evolve in the face of stress.
Author: Orna Resnekov
Publisher: Springer Science & Business Media
ISBN: 3642609295
Category : Science
Languages : en
Pages : 276
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Book Description
Many important cellular processes rely on posttranscriptional control of gene expression. This book describes the mechanisms of gene expression at this level that occur in the cytoplasm of prokaryotes and eukaryotes. Several introductory chapters discuss the general principles of translation and mRNA stability. The interactions of mature mRNA with the translational machinery, the components of mRNA degradation and antisense RNA are surveyed. Subsequent chapters discuss protein folding, transport, modification and degradation. The book is an invaluable source of information for both newcomers and those wishing an overview of the field.
