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Inhibition of Arp2/3 Complex After ADP-ribosylation of Arp2 by Binary Clostridioides Toxins
Abstract: Clostridioides bacteria are responsible for life threatening infections. Here, we show that in addition to actin, the binary toxins CDT, C2I, and Iota from Clostridioides difficile, botulinum, and perfrigens, respectively, ADP-ribosylate the actin-related protein Arp2 of Arp2/3 complex and its additional components ArpC1, ArpC2, and ArpC4/5. The Arp2/3 complex is composed of seven subunits and stimulates the formation of branched actin filament networks. This activity is inhibited after ADP-ribosylation of Arp2. Translocation of the ADP-ribosyltransferase component of CDT toxin into human colon carcinoma Caco2 cells led to ADP-ribosylation of cellular Arp2 and actin followed by a collapse of the lamellipodial extensions and F-actin network. Exposure of isolated mouse colon pieces to CDT toxin induced the dissolution of the enterocytes leading to luminal aggregation of cellular debris and the collapse of the mucosal organization. Thus, we identify the Arp2/3 complex as hitherto unknown target of clostridial ADP-ribosyltransferases
An Introduction to Molecular Biotechnology
Completely updated in line with the rapid progress made in the field, this new edition of the highly-praised textbook addresses powerful new methods and concepts in biotechnology, such as genome editing, reprogrammed stem cells, and personalized medicine. An introduction to the fundamentals in molecular and cell biology is followed by a description of standard techniques, including purification and analysis of biomolecules, cloning techniques, gene expression systems, genome editing methods, labeling of proteins and in situ-techniques, standard and high resolution microscopy. The third part focuses on key areas in research and application, ranging from functional genomics, proteomics and bio...
RNA Biochemistry and Biotechnology
RNA Biochemistry and Biotechnology describes various aspects of nucleic acid and protein structure, mainly RNA structure and proteins, interacting with specific RNA species. Papers deal with DNA protein interactions, telomerase, aminoacyl-tRNA synthetases, elongation factor Tu, DNA repair, RNA structure, NMR technology, RNA aptamer interaction of biological macromolecules with metal ions. Two papers deal with theoretical aspects of RNA structure production and computer modelling. Many papers describe the possibility of commercial application of RNA biotechnology. One article discusses the impact of direct democracy on basic science supporting biotechnology. Readership: Advanced graduate students, Ph.D. students and young scientists as well as specialists in the field.
Security, Trust and Privacy Models, and Architectures in IoT Environments
This book is dedicated to the issues of security, trust and privacy models, and architectures in IoT environments. The authors aim to capture the latest research and contributions from academy, industry, and other stakeholders on new security models, architectures, protocols, and standards for ensuring security, privacy, and trustworthiness to IoT systems. The authors discuss the convergence of IoT, software agents, and edge computing to introduce social features into IoT systems, combining trustworthiness and reputation information collected by agents at the edge with security and privacy mechanisms. They also cover experimental and simulated campaigns that evaluate strategies to improve the security and privacy of the IoT world, and at the same time the ability to prevent and deter deceptive behaviors. The book is relevant for researchers, professionals, academics, and students.
Logic for Programming, Artificial Intelligence, and Reasoning
This book constitutes the refereed proceedings of the 11th International Conference on Logic for Programming, Artificial Intelligence, and Reasoning, LPAR 2004, held in Montevideo, Uruguay in March 2005. The 33 revised full papers presented together with abstracts of 4 invited papers were carefully reviewed and selected from 77 submissions. The papers address all current issues in logic programming, automated reasoning, and AI logics in particular description logics, fuzzy logic, linear logic, multi-modal logic, proof theory, formal verification, protocol verification, constraint logic programming, programming calculi, theorem proving, etc.
Handbook of Proteomic Methods
A compendium of thirty-four powerful techniques for identifying and analyzing the diversity of proteins expressed in cells. Thee readily reproducible proteomic methods range from general to specific techniques, and include methods for data analysis, posttranslational modification, and its variants and isoforms. Additional methods demonstrate the application of proteomics to the discovery of serological tumor markers, to identifying the determinants of sensitivity to antitumor drugs, and to specialized fields, such as endocrinology, plant biology, nephrology, and urology.
Inverse Control of Rab Proteins by Yersinia ADP-ribosyltransferase and Glycosyltransferase Related to Clostridial Glucosylating Toxins
Abstract: We identified a glucosyltransferase (YGT) and an ADP-ribosyltransferase (YART) in Yersinia mollaretii, highly related to glucosylating toxins from Clostridium difficile, the cause of antibiotics-associated enterocolitis. Both Yersinia toxins consist of an amino-terminal enzyme domain, an autoprotease domain activated by inositol hexakisphosphate, and a carboxyl-terminal translocation domain. YGT N-acetylglucosaminylates Rab5 and Rab31 at Thr52 and Thr36, respectively, thereby inactivating the Rab proteins. YART ADP-ribosylates Rab5 and Rab31 at Gln79 and Gln64, respectively. This activates Rab proteins by inhibiting GTP hydrolysis. We determined the crystal structure of the glycosyltransferase domain of YGT (YGTG) in the presence and absence of UDP at 1.9- and 3.4-Å resolution, respectively. Thereby, we identified a previously unknown potassium ion-binding site, which explains potassium ion-dependent enhanced glycosyltransferase activity in clostridial and related toxins. Our findings exhibit a novel type of inverse regulation of Rab proteins by toxins and provide new insights into the structure-function relationship of glycosyltransferase toxins
Multiagent Systems, second edition
The new edition of an introduction to multiagent systems that captures the state of the art in both theory and practice, suitable as textbook or reference. Multiagent systems are made up of multiple interacting intelligent agents—computational entities to some degree autonomous and able to cooperate, compete, communicate, act flexibly, and exercise control over their behavior within the frame of their objectives. They are the enabling technology for a wide range of advanced applications relying on distributed and parallel processing of data, information, and knowledge relevant in domains ranging from industrial manufacturing to e-commerce to health care. This book offers a state-of-the-art...
Alkali Cation Transport Systems in Prokaryotes
Alkali Cation Transport Systems in Prokaryotes is the first book that brings together the physiological, structural, and molecular biological aspects of the transport of sodium, potassium, and ammonium across the bacterial cell membrane. Sodium translocation plays a major role in energy coupling of some prokaryotes, and much of the book is devoted to new and exciting developments in this field. Over 30 experts have contributed to this excellent reference for microbiologists, biochemists, molecular biologists, cell biologists, chemotherapists, and researchers interested in bioenergetics.
