Signal Transduction Mechanisms of HAMP and PAS Domains in Bacterial Chemotaxis

Signal Transduction Mechanisms of HAMP and PAS Domains in Bacterial Chemotaxis PDF Author: Nattakan Sukomon
Publisher:
ISBN:
Category :
Languages : en
Pages : 482

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Book Description
Bacteria utilize two-component systems to respond and adapt to changes in their environments. Central to the systems are modular receptors that comprise various functional domains to detect those changes and relay signals to effector domains. HAMP (Histidine kinases, Adenylate cyclases, Methyl accepting proteins and Phosphatases) and PAS (Per-Arnt-Sim) are two of the most common domains that couple various effectors to regulate a wide range of cellular activities. HAMP domains are signal relay modules that connects input and output domains. The HAMP domain from the E. coli serine receptor Tsr has been extensively studied by using genetic techniques, which leads to a model of HAMP biphasic stability that explains the behaviors of Tsr mutant receptors. However, limited biophysical data on the Tsr HAMP are available due to the instability of the domain. In order to provide stability to the Tsr HAMP, a chimera containing Tsr spliced into the poly-HAMP domains from Pseudomonas aeruginosa Aer2 (PaAer2) was created. Within the chimera, the Tsr HAMP maintains its characteristic four-helix coiled-coil structure with the distinctively lowered melting temperature compared to the PaAer2. This chimera was used to study three well-characterized HAMP mutational phenotypes differentiated by flagella-rotation patterns and CheA kinase activities: functional counterclockwise flagella rotation [CCW(A), kinase off], functional clockwise flagella rotation (CW, kinase on), and lesion-induced counterclockwise rotation [CCW(B), kinase off]. The stabilities and structural dynamics of the three phenotypes conform to the biphasic model. The transitions between functional on and off states are mediated by helix rotations and scissor-type movements. In the lesion-induced kinase off, the AS1 helices dissociate from the bundle while the AS2 helices form a two-helix colied coil. Overall, this study provides insights into relationships between HAMP conformational behaviors and their corresponding functional outputs. PAS domains are sensor motifs that are critical in signal transductions of prokaryotic and eukaryotic sensory proteins including chemoreceptors. Vibrio cholerae Aer2 (VcAer2), a PaAer2 homolog, has been shown to mediate responses to oxygen through the heme-binding PAS domains. Substitution of the conserved Trp 276 in the PAS2 domain to Leu abolished the O2-stabilizing ability, which corroborates its O2-ligating role. The crystal structure of the VcAer2 W276L is highly similar to the CN-bound PAS domain from PaAer2, suggesting the structure of the W276L mutant might represent the ligand-binding state. VcAer2 can serve as a promising alternative to E. coli Aer or PaAer2 for investigating PAS-mediated chemotaxis.

Signal Transduction Mechanisms of HAMP and PAS Domains in Bacterial Chemotaxis

Signal Transduction Mechanisms of HAMP and PAS Domains in Bacterial Chemotaxis PDF Author: Nattakan Sukomon
Publisher:
ISBN:
Category :
Languages : en
Pages : 482

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Book Description
Bacteria utilize two-component systems to respond and adapt to changes in their environments. Central to the systems are modular receptors that comprise various functional domains to detect those changes and relay signals to effector domains. HAMP (Histidine kinases, Adenylate cyclases, Methyl accepting proteins and Phosphatases) and PAS (Per-Arnt-Sim) are two of the most common domains that couple various effectors to regulate a wide range of cellular activities. HAMP domains are signal relay modules that connects input and output domains. The HAMP domain from the E. coli serine receptor Tsr has been extensively studied by using genetic techniques, which leads to a model of HAMP biphasic stability that explains the behaviors of Tsr mutant receptors. However, limited biophysical data on the Tsr HAMP are available due to the instability of the domain. In order to provide stability to the Tsr HAMP, a chimera containing Tsr spliced into the poly-HAMP domains from Pseudomonas aeruginosa Aer2 (PaAer2) was created. Within the chimera, the Tsr HAMP maintains its characteristic four-helix coiled-coil structure with the distinctively lowered melting temperature compared to the PaAer2. This chimera was used to study three well-characterized HAMP mutational phenotypes differentiated by flagella-rotation patterns and CheA kinase activities: functional counterclockwise flagella rotation [CCW(A), kinase off], functional clockwise flagella rotation (CW, kinase on), and lesion-induced counterclockwise rotation [CCW(B), kinase off]. The stabilities and structural dynamics of the three phenotypes conform to the biphasic model. The transitions between functional on and off states are mediated by helix rotations and scissor-type movements. In the lesion-induced kinase off, the AS1 helices dissociate from the bundle while the AS2 helices form a two-helix colied coil. Overall, this study provides insights into relationships between HAMP conformational behaviors and their corresponding functional outputs. PAS domains are sensor motifs that are critical in signal transductions of prokaryotic and eukaryotic sensory proteins including chemoreceptors. Vibrio cholerae Aer2 (VcAer2), a PaAer2 homolog, has been shown to mediate responses to oxygen through the heme-binding PAS domains. Substitution of the conserved Trp 276 in the PAS2 domain to Leu abolished the O2-stabilizing ability, which corroborates its O2-ligating role. The crystal structure of the VcAer2 W276L is highly similar to the CN-bound PAS domain from PaAer2, suggesting the structure of the W276L mutant might represent the ligand-binding state. VcAer2 can serve as a promising alternative to E. coli Aer or PaAer2 for investigating PAS-mediated chemotaxis.

Signal Transduction Mechanisms of PAS and HAMP Domains

Signal Transduction Mechanisms of PAS and HAMP Domains PDF Author: Michael V. Airola
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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Book Description
The focus of my dissertation is on the signaling mechanisms employed by PAS and HAMP domains, which are widespread signaling modules that coordinate cellular metabolism with external stimuli. A subset of PAS domains directly sense external stimuli, through an associated cofactor or ligand, and regulate the activity of an attached effector domain. In contrast, HAMP domains do not sense external stimuli and serve as signal relay modules. They are typically associated with the membrane and relay extracellular signals into intracellular responses. A subset of HAMP domains, which occur in poly-HAMP chains, are not associated with the membrane and differ from canonical HAMP domains in the region responsible for signal input. To investigate HAMP domain signal transduction I have used the soluble receptor Aer2 as a model system. A unifying mechanism for HAMP domain signal transduction has yet to emerge, mainly due to lack of structural information. In chapter 1, I present the crystal structure of a 3-unit poly-HAMP chain from Aer2. Two distinct HAMP conformations were identified and a new model for signal transduction is presented. In Appendix 1, I present data that defines essential features of membrane associated HAMP domains. The results indicate that a signature motif: DExG, is required for HAMP domains to receive signal input across the membrane. PAS and HAMP domains can occur within the same protein. The best-studied example is the E. coli aerotaxis receptor Aer, where direct side-on PAS and HAMP domain interactions propagate signals downstream. In Chapter 3, I present a model for PAS and HAMP domain signal transduction in Aer2 that does not involve direct sideon interactions. This represents a new paradigm for applicable to successive PAS and HAMP domains and other similar signaling systems. One recent controversy, in the mammalian circadian clock, is the identification of two core clock genes, PER2 and nPAS2, as heme-binding PAS proteins. A complicated feedback mechanism has been suggested where cycles in heme availability feedback to regulate the activity of PER2 and nPAS2. In chapter 2, I present data that PER2-heme interactions are non-specific and not biologically relevant to the mammalian circadian clock.

Signal Transduction

Signal Transduction PDF Author: Bastien D. Gomperts
Publisher: Gulf Professional Publishing
ISBN: 9780122896323
Category : Medical
Languages : en
Pages : 444

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Book Description
Signal Transduction is a text reference on cellular signalling processes. Starting with the basics, it explains how cells respond to external cues (hormones, cytokines, neurotransmitters, adhesion molecules, extracellular matrix etc), and shows how these inputs are integrated and co-ordinated. The first half of the book provides the conceptual framework, explaining the formation and action of second messengers, particularly cyclic nucleotides and calcium, and the mediation of signal pathways by GTP-binding proteins. The remaining chapters deal with the formation of complex signalling cascades employed by cytokines and adhesion molecules, starting at the membrane and ending in the nucleus, there to regulate gene transcription. In this context, growth is an important potential outcome and this has relevance to the cellular transformations that underlie cancer. The book ends with a description at the molecular level of how signalling proteins interact with their environment and with each other through their structural domains. Each main topic is introduced with a historical essay, detailing the sources, key observations and experiments that set the scene for recent and current work.

Signal Transduction Mechanisms

Signal Transduction Mechanisms PDF Author: J.A. Barnes
Publisher: Springer Science & Business Media
ISBN: 1461520150
Category : Science
Languages : en
Pages : 320

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Book Description
This volume contains the proceedings of an International Symposium on `Second Messenger Systems - Molecular, Cellular and Behavioural Aspects', which was held at Tobago on June 16-17, 1994. The interaction of an extracellular agonist (First Messenger) with its plasma membrane receptor leads to the transmission of a signal across the cell membrane and results in the production and/or activation of other signalling molecules (Second Messengers). These Second Messengers control the action of many protein kinases and protein phosphatases and so lead to cellular responses. Although the biochemical basis of the transduction of signals in the main signalling systems in eukaryotic cells is probably largely known, intensified research is ongoing in the following areas: the discovery of specific substrates for many protein kinases, elucidation of the biological significance of the differential tissue expression and heterogeneity of many signalling proteins, and the unravelling of diverse interactions (such as signal potentiation, synergism, antagonism and neuronal co-transmission) between signalling systems. As knowledge from such studies accumulates, it is becoming clear that the `cross talk' interactions between signalling systems are important features of dynamic cell regulation. This volume is designed to summarize some aspects of the current work on various Second Messenger Systems and the integration of signals with respect to plasma membrane receptors. Second Messenger generation and degradation, protein kinase and phosphatase, cell cycle control, and cellular learning and memory.

Two-component Signal Transduction

Two-component Signal Transduction PDF Author: James A. Hoch
Publisher: Amer Society for Microbiology
ISBN: 9781555810894
Category : Medical
Languages : en
Pages : 488

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Book Description
The human enteroviruses, particularly the polio viruses, have had a significant role in the history of medicine and microbiology; and continue to cause clinical problems, as well as provide targets for molecular investigation. This book offers a link between the basic science and clinical medicine.

Histidine Kinases in Signal Transduction

Histidine Kinases in Signal Transduction PDF Author: Masayori Inouye
Publisher: Elsevier
ISBN: 0080534015
Category : Science
Languages : en
Pages : 539

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Book Description
Living cells are constantly sensing environmental changes, and their abilities to sense these changes and adapt to them are essential for their survival. In bacteria, histidine kinases are the major sensors for these environmental stresses, enabling cells to adapt to new growth conditions. Written by leading experts in the field, this book provides an up-to-date and comprehensive review on the structure and function of histidine kinases. It also provides extensive information on the physiological roles of histidine kinases in bacteria and eukaryotes. An an essential reference for cell biologists, microbiologists, molecular biologists, and biochemists interested in signal transduction. Experimental biologists and pharmacologists studying signal transduction systems in living organisms will also find it a valuable research tool. - The first comprehensive book on the roles of histidine kinases in cells - 23 in-depth chapters written by leading experts in the field - Describes the most recent advances in the field of signal transduction

Trends in Signal Transduction Research

Trends in Signal Transduction Research PDF Author: Jennifer N. Meyers
Publisher: Nova Publishers
ISBN: 9781600213755
Category : Medical
Languages : en
Pages : 270

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Book Description
Signal transduction is any process by which a cell converts one kind of signal or stimulus into another. Processes referred to as signal transduction often involve a sequence of biochemical reactions inside the cell, which are carried out by enzymes and linked through second messengers. In many transduction processes, an increasing number of enzymes and other molecules become engaged in the events that proceed from the initial stimulus. Responses of cells to environmental signals, toxins and stressors have profound implications for diverse aspects of human health and disease including development, cystic fibrosis, diabetes, asthma, heart, autoimmune diseases and cancer. The delineation of the signal transduction pathways affected in these and other complex human diseases are likely to present new avenues for therapeutic intervention and understanding of human disease mechanisms.

Molecular Mechanisms of Signal Transduction

Molecular Mechanisms of Signal Transduction PDF Author: Johannes Lukas Bos
Publisher: IOS Press
ISBN: 9781586030162
Category : Science
Languages : en
Pages : 298

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Book Description
This book contains overviews of topics that have been discussed. It includes contributions from leading experts in the field on small GTPases, protein kinesis, receptors and transcription factors. A particular focus was the influence of oxygen radicals on signalling processes. It also contains the contributions of scientists early in their career, who have made an excellent contribution to the institute.

Signal Transduction and Human Disease

Signal Transduction and Human Disease PDF Author: Toren Finkel
Publisher: Wiley-Liss
ISBN: 0471448370
Category : Science
Languages : en
Pages : 488

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Book Description
This book uniquely relates the broad impact of signal transduction research on the understanding and treatment of human disease. There have been significant advances in the area of signaling in disease processes, yet no resource presently connects these advances with understanding of disease processes and applications for novel therapeutics. Given the emphasis on translational research and biological relevance in biotechnology, and, conversely, the importance of molecular approaches for clinical research, it is evident that a single resource bridging signaling research and human disease will be invaluable.

Two-component Systems in Bacteria

Two-component Systems in Bacteria PDF Author: Roy Gross
Publisher: Caister Academic Press Limited
ISBN: 9781908230089
Category : Science
Languages : en
Pages : 0

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Book Description
Current information on two-component systems in bacteria including structure-function analysis, sensing mechanisms, atypical two-component systems, stress responses, developmental processes, virulence and symbiosis.