FUNCTIONAL ANALYSIS OF THE BACTERIAL MACRODOMAIN PROTEIN YMDB AND ITS INTERACTION WITH RIBONUCLEASE III PDF Download
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Author: Samridhdi Paudyal
Publisher:
ISBN:
Category :
Languages : en
Pages : 232
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Book Description
The Escherichia coli ymdB gene encodes a ~19 kDa protein that binds ADP-ribose (ADPR) and metabolites related to NAD+. As such, it has been termed a macrodomain protein, referring to a conserved fold that binds ADPR. YmdB can catalyze the hydrolysis of O-acetyl-ADP-ribose (OAADPR), forming acetate and ADPR. OAADPR is a product of sirtuin action on lysine-acetylated proteins, which involves NAD+ as a cosubstrate. There is evidence that YmdB interacts with other proteins, including the conserved enzyme, ribonuclease III. Ribonuclease III (RNase III) is a double-strand(ds)-specific enzyme that processes diverse RNA precursors in bacterial cells to form the mature, functional forms that participate in protein synthesis and gene regulation. RNase III is involved in the maturation, turnover, and action of small noncoding RNAs (sRNAs), which play key roles in regulating bacterial gene expression in response to environmental inputs and changes in growth conditions. A mass-spectroscopy-based analysis of the E. coli proteome has shown that YmdB and RNase III interact in vivo. However, the functional importance of this interaction is not known. There is preliminary evidence that YmdB regulates RNase III activity during specific stress inputs. Thus, during cellular entry into stationary phase (nutrient limitation), or during the cold shock response, YmdB levels increase, which is correlated with a downregulation of RNase III activity. Inhibition of RNase III may alter the maturation and turnover of sRNAs, as well as other RNAs, during the adaptive response to stress. However, it is unclear whether the inhibition is a direct or indirect effect of YmdB on RNase III activity. Moreover, since YmdB binds ADPR, this (or related) metabolite may influence RNase III activity in an YmdB-dependent manner. If the YmdB-RNase III interaction in fact regulates RNase III, this interaction may connect post-transcriptional regulatory pathways with the cellular metabolic state, as reflected by NAD+ and ADPR levels. The goal of this project is to characterize the YmdB interaction with RNase III, with the long-range goal of understanding the mechanism and role of YmdB regulation of RNase III. Since both YmdB and RNase III are conserved bacterial proteins, characterization of YmdB and its influence on RNase III activity would provide insight on a conserved interaction in bacterial cells in general as well as reveal a potentially novel mechanism of post-transcriptional gene regulation.
Author: Samridhdi Paudyal
Publisher:
ISBN:
Category :
Languages : en
Pages : 232
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Book Description
The Escherichia coli ymdB gene encodes a ~19 kDa protein that binds ADP-ribose (ADPR) and metabolites related to NAD+. As such, it has been termed a macrodomain protein, referring to a conserved fold that binds ADPR. YmdB can catalyze the hydrolysis of O-acetyl-ADP-ribose (OAADPR), forming acetate and ADPR. OAADPR is a product of sirtuin action on lysine-acetylated proteins, which involves NAD+ as a cosubstrate. There is evidence that YmdB interacts with other proteins, including the conserved enzyme, ribonuclease III. Ribonuclease III (RNase III) is a double-strand(ds)-specific enzyme that processes diverse RNA precursors in bacterial cells to form the mature, functional forms that participate in protein synthesis and gene regulation. RNase III is involved in the maturation, turnover, and action of small noncoding RNAs (sRNAs), which play key roles in regulating bacterial gene expression in response to environmental inputs and changes in growth conditions. A mass-spectroscopy-based analysis of the E. coli proteome has shown that YmdB and RNase III interact in vivo. However, the functional importance of this interaction is not known. There is preliminary evidence that YmdB regulates RNase III activity during specific stress inputs. Thus, during cellular entry into stationary phase (nutrient limitation), or during the cold shock response, YmdB levels increase, which is correlated with a downregulation of RNase III activity. Inhibition of RNase III may alter the maturation and turnover of sRNAs, as well as other RNAs, during the adaptive response to stress. However, it is unclear whether the inhibition is a direct or indirect effect of YmdB on RNase III activity. Moreover, since YmdB binds ADPR, this (or related) metabolite may influence RNase III activity in an YmdB-dependent manner. If the YmdB-RNase III interaction in fact regulates RNase III, this interaction may connect post-transcriptional regulatory pathways with the cellular metabolic state, as reflected by NAD+ and ADPR levels. The goal of this project is to characterize the YmdB interaction with RNase III, with the long-range goal of understanding the mechanism and role of YmdB regulation of RNase III. Since both YmdB and RNase III are conserved bacterial proteins, characterization of YmdB and its influence on RNase III activity would provide insight on a conserved interaction in bacterial cells in general as well as reveal a potentially novel mechanism of post-transcriptional gene regulation.
Author: Alexandra Kimberly Smith
Publisher:
ISBN:
Category :
Languages : en
Pages : 69
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Book Description
Gene expression pathways exhibit many "twists and turns," with theoretically numerous ways in which the pathways can be regulated by both negative and positive feedback mechanisms. A key step in gene expression is RNA maturation (RNA processing), which in the bacterial cell can be accomplished through RNA binding and enzymatic cleavages. The well-characterized bacterial protein Ribonuclease III (RNase III), is a conserved, double-stranded(ds)-specific ribonuclease. In the gram-negative bacterium Escherichia coli, RNase III catalytic activity is subject to both positive and negative regulation. A recent study has indicated that an E. coli protein, YmdB, may negatively regulate RNase III catalytic activity. It has been proposed that YmdB inhibition of RNase III may be part of an adaptive, post-transcriptional physiological response to cellular stress. In E. coli, the model organism in this study, YmdB protein is encoded by the single ymdB gene, and has a predicted molecular mass of ~18.8 kDa. YmdB has been classified as a macrodomain protein, as it exhibits a characteristic fold that specifically provides an ADP-ribose (ADPR) binding site. While YmdB can bind ADPR with good affinity, there may be additional ligands for the binding site. Thus, YmdB protein may interact with other components in the cell, which in turn could modulate the interaction of YmdB with RNase III. In previous research conducted within the Nicholson laboratory at Temple University, affinity-purified Escherchia coli(Ec) YmdB and Aquifex aeolicus (Aa) YmdB were found to exhibit ribonucleolytic activity. This observation initiated the long-term goal of learning how YmdB regulates RNase III, and how the ribonucleolytic activity of YmdB may be involved in this process. The specific goal of this thesis project was to further characterize the ribonucleolytic activity of Ec-YmdB through site-specific mutational analysis. Mutations were introduced into a proposed adenine-binding pocket previously identified by crystallography and by molecular modeling. The adenine-binding pocket is a region within the macrodomain fold where ADP-ribose could bind. The mutations were examined for their effect on Ec-YmdB cleavage of a model RNA, R1.1. The results of this study will contribute to the development of a model describing how the ribonucleolytic activity of YmdB is regulated.
Author: John Harry Caufield
Publisher:
ISBN:
Category : Bacteriophages
Languages : en
Pages : 315
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Book Description
The emergence of genomics as a discrete field of biology has changed humanity's understanding of our relationship with bacteria. Sequencing the genome of each newly-discovered bacterial species can reveal novel gene sequences, though the genome may contain genes coding for hundreds or thousands of proteins of unknown function (PUFs). In some cases, these coding sequences appear to be conserved across nearly all bacteria. Exploring the functional roles of these cases ideally requires an integrative, cross-species approach involving not only gene sequences but knowledge of interactions among their products. Protein interactions, studied at genome scale, extend genomics into the field of interactomics. I have employed novel computational methods to provide context for bacterial PUFs and to leverage the rich genomic, proteomic, and interactomic data available for hundreds of bacterial species. The methods employed in this study began with sets of protein complexes. I initially hypothesized that, if protein interactions reveal protein functions and interactions are frequently conserved through protein complexes, then conserved protein functions should be revealed through the extent of conservation of protein complexes and their components. The subsequent analyses revealed how partial protein complex conservation may, unexpectedly, be the rule rather than the exception. Next, I expanded the analysis by combining sets of thousands of experimental protein-protein interactions. Progressing beyond the scope of protein complexes into interactions across full proteomes revealed novel evolutionary consistencies across bacteria but also exposed deficiencies among interactomics-based approaches. I have concluded this study with an expansion beyond bacterial protein interactions and into those involving bacteriophage-encoded proteins. This work concerns emergent evolutionary properties among bacterial proteins. It is primarily intended to serve as a resource for microbiologists but is relevant to any research into evolutionary biology. As microbiomes and their occupants become increasingly critical to human health, similar approaches may become increasingly necessary.
Author: Ilana L. B. C. Camargo
Publisher: Frontiers Media SA
ISBN: 2889662845
Category : Science
Languages : en
Pages : 570
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Book Description
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Author: Joseph E. Alouf
Publisher: Elsevier
ISBN: 0080456987
Category : Science
Languages : en
Pages : 1072
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Book Description
This book describes the major achievements and discoveries relevant to bacterial protein toxins since the turn of the new century illustrated by the discovery of more than fifty novel toxins (many of them identified through genome screening). The establishment of the three-dimensional crystal structure of more than 20 toxins during the same period offers deeper knowledge of structure-activity relationships and provides a framework to understand how toxins recognize receptors, penetrate membranes and interact with and modify intracellular substrates. - Edited by two of the most highly regarded experts in the field from the Institut Pasteur, France - 14 brand new chapters dedicated to coverage of historical and general aspects of toxinology - Includes the major toxins of both basic and clinical interest are described in depth - Details applied aspects of toxins such as therapy, vaccinology, and toolkits in cell biology - Evolutionary and functional aspects of bacterial toxins evaluated and summarized - Toxin applications in cell biology presented - Therapy (cancer therapy, dystonias) discussed - Vaccines (native and genetically engineered vaccines) featured - Toxins discussed as biological weapons, comprising chapters on anthrax, diphtheria, ricin etc.
