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A NATO Advanced Study Institute on "New Developments in Lipid-Protein Interactions and Receptor Function" was held on the Island of Spetsai, Greece, from August 16-27, 1992. This Institute was organized to bring together researchers in the field of membrane organization and dynamics with those actively involved in studies on receptor function, signal transduction mechanisms and gene regulation. 2 Presentations and discussions focussed on the regulation of intracellular Ca +-levels, on the second messengers derived from inositol lipids and on the specific phospholipase C isozymes involved in these processes. A major focus was on G-proteins and the effect of lipid anchors on their function. These principles of regulation were further discussed in the context of receptors for acetylcholine, lysophosphatidic acid and low-density lipoproteins. In addition, various aspects of the genomic regulation of cell growth and differentiation by transcription factors were presented. These topics were put into perspective by discussing the most recent developments in lipid-protein interactions, protein insertion into membranes, membrane lipid organization and lipid dynamics as mediated by phospholipid transfer proteins. This book presents the content of the major lectures and a selection of the most relevant of the most important topics posters. These proceedings offer a comprehensive account presented during the course of the Institute. The book is intended to make these proceedings accessible to a large audience.
Biological membranes have long been identified as key elements in a wide variety of cellular processes including cell defense communication, photosynthesis, signal transduction, and motility; thus they emerge as primary targets in both basic and applied research. This book brings together in a single volume the most recent views of experts in the area of protein–lipid interactions, providing an overview of the advances that have been achieved in the field in recent years, from very basic aspects to specialized technological applications. Topics include the application of X-ray and neutron diffraction, infrared and fluorescence spectroscopy, and high-resolution NMR to the understanding of the specific interactions between lipids and proteins within biological membranes, their structural relationships, and the implications for the biological functions that they mediate. Also covered in this volume are the insertion of proteins and peptides into the membrane and the concomitant formation of definite lipid domains within the membrane.
Free energy constitutes the most important thermodynamic quantity to understand how chemical species recognize each other, associate or react. Examples of problems in which knowledge of the underlying free energy behaviour is required, include conformational equilibria and molecular association, partitioning between immiscible liquids, receptor-drug interaction, protein-protein and protein-DNA association, and protein stability. This volume sets out to present a coherent and comprehensive account of the concepts that underlie different approaches devised for the determination of free energies. The reader will gain the necessary insight into the theoretical and computational foundations of the subject and will be presented with relevant applications from molecular-level modelling and simulations of chemical and biological systems. Both formally accurate and approximate methods are covered using both classical and quantum mechanical descriptions. A central theme of the book is that the wide variety of free energy calculation techniques available today can be understood as different implementations of a few basic principles. The book is aimed at a broad readership of graduate students and researchers having a background in chemistry, physics, engineering and physical biology.
In this book, renowned scientists describe how cholesterol interacts with various proteins. Recent progress made in the high-resolution visualization of cholesterol-protein interactions using crystallography and cryogenic electron microscopy has substantially advanced the knowledge of critical features. These features enable specific recognition of the cholesterol molecule by proteins, a process that was built on earlier studies using binding assays, computational modeling and site-directed mutagenesis. Direct Mechanisms in Cholesterol Modulation of Protein Function offers comprehensive insights into the current understanding of cholesterol-driven modulation of protein function via direct sensing. Its nine chapters are organized into two distinct parts. In the first part, the chapters introduce the reader to the general characteristics of cholesterol binding sites in proteins. This part starts with a tour into common cholesterol recognition motifs, followed by an overview of the major classes of steroid-binding proteins. It then continues with two chapters that present a comprehensive analysis of molecular and structural characteristics of cholesterol binding sites in transmembrane and soluble protein domains. In the second part of the book, examples of cholesterol binding sites and consequences of specific cholesterol recognition for protein function are presented for G protein-coupled receptors, ion channels and cholesterol-transporting proteins. The book is valuable for undergraduate and graduate students in biochemistry and nutrition, as well as basic science and medical researchers with a keen interest in the biophysical properties of cholesterol and physiological consequences of cholesterol presence in biological systems.
Protein-lipid interactions as a field of study is now a mature area, and this volume of NewComprehensive Biochemistry has been published with two objectives in mind. Firstly, to look to thefuture, and try to envisage how the subject may develop in the near to medium future. Secondly, to presentcontrasting or complementary views on the same system. For example, the acetylcholine receptor is discussedfrom a predominantly structural aspect by Barrantes, and from the kinetic standpoint by Rankin, et al. The volume not only gives an update on specific aspects of the field, but also shows the way in whichthe phenomenon of protein-lipid interactions is now seemingly infiltrating many areas of biomembraneresearch, from recombinant DNA studies, protein insertion and assembly and reconstitution considerationsto structural studies of membrane proteins.
Lipids are the most abundant organic compounds found in the brain, accounting for up to 50% of its dry weight. The brain lipidome includes several thousands of distinct biochemical structures whose expression may greatly vary according to age, gender, brain region, cell type, as well as subcellular localization. In synaptic membranes, brain lipids specifically interact with neurotransmitter receptors and control their activity. Moreover, brain lipids play a key role in the generation and neurotoxicity of amyloidogenic proteins involved in the pathophysiology of neurological diseases. The aim of this book is to provide for the first time a comprehensive overview of brain lipid structures, and to explain the roles of these lipids in synaptic function, and in neurodegenerative diseases, including Alzheimer’s, Creutzfeldt-Jakob’s and Parkinson’s. To conclude the book, the authors present new ideas that can drive innovative therapeutic strategies based on the knowledge of the role of lipids in brain disorders. Written to provide a "hands-on" approach for readers Biochemical structures explained with molecular models, and molecular mechanisms explained with simple drawings Step-by-step guide to memorize and draw lipid structures Each chapter features a content summary, up-to-date references for additional study, and a key experiment with an explanation of the technique
Genetic variations may change the structure and function of individual proteins as well as affect their interactions with other proteins and thereby impact metabolic processes dependent on protein-protein interactions. For example, cytochrome P450 proteins, which metabolize a vast array of drugs, steroids and other xenobiotics, are dependent on interactions with redox and allosteric partner proteins for their localization, stability, (catalytic) function and metabolic diversity (reactions). Genetic variations may impact such interactions by changing the splicing and/or amino acid sequence which in turn may impact protein topology, localization, post translational modifications and three dimensional structure. More generally, research on single gene defects and their role in disease, as well as recent large scale sequencing studies suggest that a large number of genetic variations may contribute to disease not only by affecting gene function or expression but also by modulating complex protein interaction networks. The aim of this research topic is to bring together researchers working in the area of drug, steroid and xenobiotic metabolism who are studying protein-protein interactions, to describe their recent advances in the field. We are aiming for a comprehensive analysis of the subject from different approaches including genetics, proteomics, transcriptomics, structural biology, biochemistry and pharmacology. Of particular interest are papers dealing with translational research describing the role of novel genetic variations altering protein-protein interaction. Authors may submit original articles, reviews and opinion or hypothesis papers dealing with the role of protein-protein interactions in health and disease. Potential topics include, but are not limited to: • Role of protein-protein interactions in xenobiotic metabolism by cytochrome P450s and other drug metabolism enzymes. • Role of classical and novel interaction partners for cytochrome P450-dependent metabolism which may include interactions with redox partners, interactions with other P450 enzymes to form P450 dimers/multimers, P450-UGT interactions and proteins involved in posttranslational modification of P450s. • Effect of genetic variations (mutations and polymorphisms) on metabolism affected by protein-protein interactions. • Structural implications of mutations and polymorphisms on protein-protein interactions. • Functional characterization of protein-protein interactions. • Analysis of protein-protein interaction networks in health and disease. • Regulatory mechanisms governing metabolic processes based on protein-protein interactions. • Experimental approaches for identification of new protein-protein interactions including changes caused by mutations and polymorphisms.
This book describes the current state of knowledge in receptor function in the development of new drugs. Science is on the verge of viewing effector molecules and other regulatory sites as therapeutic targets for the amelioration of human and animal disease. The book reviews the availability of state-of-the-art tools that allow measurement of interactions and afford unprecedented insight into the biomolecular interactions that present novel approaches to drug design.