Cholesterol Binding And Cholesterol Transport Proteins

Knowledge of cholesterol and its interaction with protein molecules is of fundamental importance in both animal and human biology. This book contains 22 chapters, dealing in depth with structural and functional aspects of the currently known and extremely diverse unrelated families of cholesterol-binding and cholesterol transport proteins. By drawing together this range of topics the Editor has attempted to correlate this broad field of study for the first time. Technical aspects are given considerable emphasis, particularly in relation cholesterol reporter molecules and to the isolation and study of membrane cholesterol- and sphingomyelin-rich "raft" domains. Cell biological, biochemical and clinical topics are included in this book, which serve to emphasize the acknowledged and important benefits to be gained from the study of cholesterol and cholesterol-binding proteins within the biomedical sciences and the involvement of cholesterol in several clinical disorders. It is hoped that by presenting this topic in this integrated manner that an appreciation of the fact that there is much more that needs to be taken into account, studied and understood than the widely discussed "bad and good cholesterol" associated, respectively, with the low- and high-density lipoproteins, LDL and HDL.

Non-vesicular intracellular cholesterol transport is an important mechanism for maintaining membrane cholesterol homeostasis. Recent reports of studies directed at soluble cholesterol transport proteins indicate that aberrant expression of the START proteins may contribute to disease states associated with disorders in cholesterol homeostasis. This is an exciting new direction in the field and the purpose of this book will be to highlight the current research directed at potential roles for the START family in diabetes, cancer and atherogenesis. This book also provides a personal and historical perspective of the discovery-to-publication journey that the authors had for their particular START domain family member. The goal will be to provide perspectives to graduate students, post-doctoral fellows and endocrinology fellows on the research discovery process.

INTRODUCTION AND RATIONALE FOR INTRACELLULAR CHOLESTEROL TRAFFICKING This volume is an elaboration of an earlier small meeting held in St. Louis, Missouri. In April 1997, many of the authors met for a two-day meeting devoted entirely to intracellular cholesterol trafficking. The rationale for this meeting was that investigators interested in this topic worked in a variety of fields, and rarely, if ever, all met together. Everybody knew each other's papers but mostly worked in isolation from one another. Understanding of cholesterol trafficking also appeared to have reached the point where it would start to rapidly expand beyond these few laboratories. Understanding of cholesterol trafficking was moving from a largely descriptive science into the molecular age. It seemed a good time to get together and see how much we agreed upon up to this point. More authors contributed to this volume than attended the St. Louis meeting. That meeting was generously funded by grants from Bristol-Myers Squibb, Merck and Company and Parke-Davis, however, the total funding available limited the size of the meeting. For the book, we are not so limited and have tried to be as inclusive as possible and pretty much invited everyone who is presently active in this area. We were quite fortunate to successfully recruit the authors we sought for each of these chapters. The authors and their contributions can be organized by particular interests and particular areas of expertise.

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.

A number of clinical and epidemiological studies have shown that disorders of lipoprotein metabolism constitute one of the most important risk factors for the development of atherosclerosis and coronary heart disease. This volume examines the state of the art of lipoprotein subclass metabolism and its relation to these diseases. The authors also report on new developments concerning the role of lipoprotein recptors, macrophages and apolipoprotein E polymorphism in cholesterol homeostasis. The combination of general outline form and very specific aspects of cholesterol transport will interest those in other disciplines following developments in the field, as well as those directly involved in lipoprotein research.

Examines new research on the role of cholesterol in regulating ion channels and receptors and its effect on health Drawing together and analyzing all the latest research findings, this book explores the role of cholesterol in the regulation of ion channels and receptors, including its pathological effects. It is the first book to comprehensively describe the complex mechanisms by which cholesterol regulates two major classes of membrane proteins. Moreover, it sheds new light on how cholesterol affects essential cellular functions such as the contraction of the heart, propagation of nerve impulses, and regulation of blood pressure and kidney function. Written and edited by leading pioneers in the field, Cholesterol Regulation of Ion Channels and Receptors is divided into three parts: Part I, Cholesterol Regulation of Membrane Properties, introduces the heterogeneity of cholesterol distribution in biological membranes and the physical and biological implications of the formation of cholesterol-rich membrane domains. Part II, Cholesterol Regulation of Ion Channels, examines the mechanisms underlying cholesterol sensitivities of ion channels, including the regulation of ion channels by cholesterol as a boundary lipid. Part III, Cholesterol Regulation of Receptors, explores the latest discoveries concerning how cholesterol regulates distinct types of receptors, including G-protein coupled receptors, LDL and scavenger receptors, and innate immune system receptors. Increased levels of cholesterol represent a major health risk. Understanding cholesterol regulation of ion channels and receptors is essential for facilitating the development of new therapeutic strategies to alleviate the impact of pathological cholesterol conditions. With this book as their guide, readers have access to the most current knowledge in the field.

In this Handbook of Experimental Pharmacology on “High Density Lipoproteins – from biological understanding to clinical exploitation” contributing authors (members of COST Action BM0904/HDLnet) summarize in more than 20 chapters our current knowledge on the structure, function, metabolism and regulation of HDL in health and several diseases as well as the status of past and ongoing attempts of therapeutic exploitation. The book is of interest to researchers in academia and industry focusing on lipoprotein metabolism, cardiovascular diseases and immunology as well as clinical pharmacologists, cardiologists, diabetologists, nephrologists and other clinicians interested in metabolic or inflammatory diseases.