Protein Lipidation In Health And Disease

The purpose of this book is to introduce the readers on the perspective of the role that unsaturated fatty acids and complex lipids play on health and disease. Bioactive lipids can be modified affecting membrane composition, structure and fluidity in addition to changes in cell signaling associated to lipid-protein (membrane receptors) interactions, issues that are addressed by the authors. This book analyzes key topics involving bioactive lipids and their role in normal signaling and the mechanisms of disease. The book navigates from structural studies of oxidized and non-oxidized lipids to the reactions and cell signaling processes that bioactive lipids play in cardiovascular and neurodegenerative diseases. The book contains the recent advances reported in the literature about lipidomics as well as the role that lipid-derived compounds exert on unfolded protein response and lipid metabolism and disease. This book represents a state of the art introduction to lipid metabolism from a biochemical to an in vivo overview being an useful tool for students and investigators. We hope the mechanistic observations on the role of bioactive lipids in health and disease serve a perspective to improve the existing treatments or propose new lipid-based pharmacology

In light of the increasing importance of these proteins and their ligands for our understanding of cellular growth, differentiation, and development, as well as of diseases such as obesity, insulin resistance, atherosclerosis, cancer, and inflammation, a team of internationally renowned editors and authors have compiled here the very first comprehensive book on these topics. They describe fatty acid-activated transcription factors as well as membrane and soluble fatty acid transporters, covering such aspects as structure and function, lipid-protein interaction, delivery of ligands, and the roles of these proteins in gene expression pertaining to the homeostatic and diseased states of cells and organs. Incorporating recent findings, this is indispensable for basic scientists, health professionals in industry and clinics as well as postgraduate students. Contributors among others: N.A. Abumrad, J.E. Schaffer, G. Schmitz, N.J. Brunskill, J. Storch, U. Seedorf, S. Mandrup, C.N.A. Palmer, T. Perlmann, H.I. Nebb, J. Bar-Tana, H. Kondo, C. Wolfrum, C. Kerkhoff , S. Farmer, E.J. Murphy, J.F.C. Glatz, P. Besnard, J.M. Stewart, A. Meirhaeghe, J. Plutzky, W. Wahli, R.A. Roberts

​Protein conversion from a water-soluble native conformation to the insoluble aggregates and fibrils, which can deposit in amyloid plaques, underlies more than 20 human diseases, representing a major public health problem and a scientific challenge. Such a conversion is called protein misfolding. Protein misfolding can also involve errors in the topology of the folded proteins and their assembly in lipid membranes. Lipids are found in nearly all amyloid deposits in vivo, and can critically influence protein misfolding in vitro and in vivo in many different ways. This book focuses on recent advances in our understanding of the role of lipids in modulating the misfolding of various proteins. The main emphasis is on the basic biophysical studies that address molecular basis of protein misfolding and amyloid formation, and the role of lipids in this complex process.

Concise chapters, written by experts in the field, cover a wide spectrum of topics on lipid and membrane formation in microbes (Archaea, Bacteria, eukaryotic microbes).All cells are delimited by a lipid membrane, which provides a crucial boundary in any known form of life. Readers will discover significant chapters on microbial lipid-carrying biomolecules and lipid/membrane-associated structures and processes.

This volume explores techniques used to detect lipids attached to proteins, to analyze the function of lipid modifications, and to characterize the enzymes that add and remove lipids from proteins. The book is organized into seven parts: Part One describes chemically-based strategies to identify substrates for protein lipidation that can be applied to individual proteins or globally using proteomics. Part Two focuses on the enzymes that remove fatty acids from proteins and provides methods to monitor protein biogenesis and palmitate turnover. Part Three addresses biochemical and cellular characterization of DHHC S-acyltransferases, a family of enzymes with 23 members encoded by the human genome. Part Four presents the SwissPalm 2 database and tips on how to use it effectively. Part Five focuses on fatty acylation that occurs in the lumen of the secretory pathway. Parts Six and Seven conclude the book with methods to produce and assay lipid-modified and integral membrane proteins. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and authoritative, Protein Lipidation: Methods and Protocols is a valuable resource for experts in the field and for investigators who encounter protein lipidation through their research on a particular cellular process or favorite protein.

This book provides the first comprehensive coverage of the quickly evolving research field of membrane contact sites (MCS). A total of 16 chapters explain their organization and role and unveil the significance of MCS for various diseases. MCS, the intracellular structures where organellar membranes come in close contact with one another, mediate the exchange of proteins, lipids, and ions. Via these functions, MCS are critical for the survival and the growth of the cell. Owing to that central role in the functioning of cells, MCS dysfunctions lead to important defects of human physiology, influence viral and bacterial infection, and cause disease such as inflammation, type II diabetes, neurodegenerative disorders, and cancer. To approach such a multifaceted topic, this volume assembles a series of chapters dealing with the full array of research about MCS and their respective roles for diseases. Most chapters also introduce the history and the state of the art of MCS research, which will initiate discussion points for the respective types of MCS for years to come. This work will appeal to all cell biologists as well as researchers on diseases that are impacted by MCS dysfunction. Additionally, it will stimulate graduate students and postdocs who will energize, drive, and develop the research field in the near future.

It is hard to think of a protein in eukaryotic cells that does not undergo some type of posttranslational modification. The covalent attachment of l- ids to proteins, protein lipidation, occurs for a few thousand proteins. Several functions for protein lipidation are known. Protein lipids may target proteins to specific cellular membranes, they may serve as molecular switches that allow cytosol-to-membrane transfer, they may direct protein–protein compl- ation, and they may stabilize protein structure. In cases such as the fatty a- lation of intracellular loops of transmembrane proteins, the funtions of the protein lipidations are not known. This volume—Protein Lipidation Protocols—provides detailed meth- ologies for the study of these processes. Since this is a rapidly growing field, many new experimental techniques have been developing over the past few years. All of the experimental techniques described in this volume have emerged during this time. The editor has made a special effort to include only those techniques that have not been previously described in a “hands-on” f- mat.

Protein degradation has been identified as a major mechanism for the regulation of cellular functions. Not surprisingly, its deregulation is implied in almost any pathological condition. This book describes how aged proteins are eliminated during cell metabolism, how cell proliferation is regulated by protein degradation and how its deregulation can contribute to the development of cancer, how protein degradation is modified during normal and abnormal aging, in particular with regard to Alzheimer's disease and other degenerative diseases of the brain and central nervous system. Attempts aiming at correcting these pathologies by interfering with deviations of the normal pathway of protein degradation are also treated.

This volume is organized around the three major classes of lipids that have been identified in covalent attachment to proteins in eukaryotic cells: isoprenoids, saturated fatty acyl groups and glycosylphosphatidylinositol ( GPI ).