Structure-function Relationship of K+ Ion Channel Toxins


Book Description

"This is a Ph.D. dissertation. Many fundamental processes underlying nerve and muscle excitation, hormone secretion, learning and memory, cell proliferation, sensory transduction and regulation of blood pressure and osmotic balance, are attributed to a div"




From Peptide and Protein Toxins to Ion Channel Structure/Function and Drug Design


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.







Pharmacology of Potassium Channels


Book Description

The aim of the present book is to comprehensively review current advances in understanding of genetics, structural biology, pharmacology of potassium channels and their roles in disease as well as to identify current gaps in knowledge. The ultimate goal is to provide a scientific foundation for better understanding of modulatory mechanisms and pharmacology of potassium channels and to use this understanding to drive future drug discovery. This book will be a must-have for academic and industrial scientists interested in physiology, pharmacology, pathology and structure-functional relationships of ion channels. The book will also be helpful for lecturers and students in the college and university classrooms, as well as for anyone interested in the state-of-the art in modern cell biology, physiology and pharmacology.




Ion Channels


Book Description

Ion channels are crucial components of living cells. Situated in the cell's membranes. they allow particular ions to pass from one side of the membrane to the other. In recent years the patch clamp technique has allowed the activity of individual channels to be measured, and recombinant DNA technology has led to fascinating detail on their structure. Together, these technical advances have produced a great flowering of knowledge and understanding about the subject, itself leading to further breakthroughs in science and medicine. Ion Channels provides an introduction to this scientific endeavour. It emphasises the molecular structure of channels as determined by gene cloning technology. This knowledge illuminates discussions of the permeability and selectivity of channels, their gating and modulation, their responses to drugs and toxins and the human diseases caused when they do not function properly.




The Structure and Function Relationship Between Guangxitoxin and the Voltage-gated Potassium Channel Kv2.1


Book Description

Proteins are the functional units of biology. They are essential in physiological processes. To achieve their functions, each protein folds into a characteristic three dimensional structure encoded by its primary amino acid sequence. Voltage-gated ion channels (VGICs) are a well-studied class of proteins which form pores in membranes permitting the conduction of ions. Voltage-gated potassium (Kv) channels are a specific subtype of VGICs in which the functional protein is tetrameric with each monomer consisting of six transmembrane (S1-S6) helices. Kv channels are all selective for potassium ions, yet are composed of many different subtypes which show sequence diversity and variation in cellular expression. With such diversity, their physiological contribution is difficult to determine without selective inhibitors of specific ion channel subtypes. Fortunately, natural sources of ion channel inhibitors have been found in venoms of animals such as tarantulas and scorpions. In this work I focused on the Kv2.1 channel and its interaction with the tarantula venom peptide Guangxitoxin (GxTX). In the subsequent chapters it will first introduce the physiological context of Kv2.1 activity. Functionally, Kv2.1 belongs to the delayed rectifier class of Kv channels showing sigmoidal activation in response to voltage and slow inactivation. Secondly; I will present electrophysiological measurements and chemical modification of GxTX to show the functional state of Kv2.1 modulates toxin affinity and binding kinetics. Thirdly, I will present a study using homology modeling to develop structural hypotheses of complexes of GxTX binding to the channel. Lastly, I will propose a functional mechanism for how Kv2.1 activity is modulated when GxTX is bound.




Ion Channels: Channel Chemical Biology, Engineering, and Physiological Function


Book Description

Ion Channels, Part C, Volume 653 in the Methods in Enzymology series, highlights new advances in the field with this new volume presenting interesting chapters on a variety of topics, including Nonsense suppression in ion channels, Engineering Ion Channels Using Protein Trans-splicing, Probing Ion Channel Neighborhoods Using APEX, STX based probes for NaVs, ANAP: a versatile, fluorescent probe of ion channel gating and regulation, High Throughput Screens for Small Molecule Ion Channel Modulators, Using toxins to study ion channels, Re/de-constructing ubiquitin regulation of ion channels, Tethered Peptide Toxins for Ion Channels, Voltage-Sensing Phosphatase Molecular Engineering, and more. Additional chapters cover Engineering excitable cells, Stretch and Poke Stimulation of Mechanically-Activated Ion Channels, Optical Control of STIM Channels, High Throughput Electrophysiological Evaluation of Mutant Ion Channels, Evaluating BEST1 Mutations in RPE Stem Cells, Long Read Transcript Profiling of Ion Channel Splice Variants, Permeation of Connexin Channels, Ratiometric pH indicator for melanosomes and lysosomes, and Ion channels in the epithelial cells of the choroid plexus. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Enzymology series




Encyclopedia of Metalloproteins


Book Description

In biochemistry, a metalloprotein is a generic term for a protein that contains a metal cofactor. The metal may be an isolated ion or may be coordinated with a nonprotein organic compound, such as the porphyrin found in hemoproteins. In some cases, the metal is co-coordinated with a side chain of the protein and an inorganic nonmetallic ion. This kind of protein-metal-nonmetal structure is seen in iron-sulfur clusters Metalloproteins deals with all aspects related to the intracellular and extracellular metal-binding proteins, including their structures, properties and functions. The biological roles of metal cations and metal-binding proteins are endless. They are involved in all crucial cellular activities. Many pathological conditions are related to the problematic metal metabolism. Research in metalloprotein-related topics is therefore rapidly growing, and different aspects of metal-binding proteins progressively enter curricula at Universities and even at the High School level on occasion. However, no key resource providing basic, but comprehensible knowledge on this rapidly expanding field exists. The Encyclopedia of Metalloproteins aims to bridge this gap, and will attempt to cover various aspects of metalloprotein/metalloproteomics and will deal with the different issues related to the intracellular and extracellular metal-binding proteins, including their structures, properties and functions. The goal is to cover exhaustively all catalytically and biologically crucial metal ions and to find at least one interacting protein for other metal ions. The Encyclopedia of Metalloproteins will provide a key resource for advanced undergraduate and graduate students, researchers, instructors, and professors interested in protein science, biochemistry, cell biology, and genetics.




Calcium Entry Channels in Non-Excitable Cells


Book Description

Calcium Entry Channels in Non-Excitable Cells focuses on methods of investigating the structure and function of non-voltage gated calcium channels. Each chapter presents important discoveries in calcium entry pathways, specifically dealing with the molecular identification of store-operated calcium channels which were reviewed by earlier volumes in the Methods in Signal Transduction series. Crystallographic and pharmacological approaches to the study of calcium channels of epithelial cells are also discussed. Calcium ion is a messenger in most cell types. Whereas voltage gated calcium channels have been studied extensively, the non-voltage gated calcium entry channel genes have only been identified relatively recently. The book will fill this important niche.




Voltage Gated Sodium Channels


Book Description

A number of techniques to study ion channels have been developed since the electrical basis of excitability was first discovered. Ion channel biophysicists have at their disposal a rich and ever-growing array of instruments and reagents to explore the biophysical and structural basis of sodium channel behavior. Armed with these tools, researchers have made increasingly dramatic discoveries about sodium channels, culminating most recently in crystal structures of voltage-gated sodium channels from bacteria. These structures, along with those from other channels, give unprecedented insight into the structural basis of sodium channel function. This volume of the Handbook of Experimental Pharmacology will explore sodium channels from the perspectives of their biophysical behavior, their structure, the drugs and toxins with which they are known to interact, acquired and inherited diseases that affect sodium channels and the techniques with which their biophysical and structural properties are studied.