Cholesterol Modulation Of Protein Function

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.

In this book, renowned scientists describe the role of steroid chirality and modification of lipid membrane physical properties in the modulation of G protein-coupled receptors and ion channels. The application of commonly-used technical approaches such as mass spectrometry and nucleic magnetic resonance transfer spectroscopy for studies on cholesterol distribution and alteration of lipid bilayer characteristics is also discussed. This book offers comprehensive insights into the current understanding of cholesterol-driven modulation of protein function via mechanisms that extend beyond lipid-protein direct interactions. In the first part, the chapters introduce the reader to the use of the chemical derivatives of cholesterol as a valuable laboratory tool in the studies of cholesterol-driven modulation of protein function. In the second part, examples of cholesterol-induced changes in membrane physical characteristics are presented and discussed in light of their multifaceted contribution to the effect of cholesterol on protein function. The book will be of interest to undergraduate and graduate students 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.

Cholesterol is an essential component of the plasma membrane. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), although a minor phospholipid, is the most abundant membrane phosphoinositide. Both lipids play key roles in a variety of cellular functions including as signalling molecules and major regulators of protein function. Studies on these important lipids have traditionally focused on the effect of each lipid individually. Accumulating evidence indicates, however, that these lipids may cross-regulate each other’s levels. Furthermore, it is becoming evident that cholesterol and PI(4,5)P2 can act together to modulate protein function and biological processes. This book provides an overview of cellular functions and molecular mechanisms in which cholesterol and PI(4,5)P2 functions extend from parallel existence to crosstalk. It includes four sections. The first section introduces the reader to cholesterol and PI(4,5)P2. The second section demonstrates the mutual influence of these two critical lipids on their levels. The third section, divided into two parts, describes the co-modulation of protein function by cholesterol and PI(4,5)P2. The first part focuses on ion channels and the second - on lipid transfer proteins. The fourth section highlights other cellular processes at the intersection of cholesterol and PI(4,5)P2 involvement. Collectively, the book portrays the emerging relationship between cholesterol and PI(4,5)P2 in a broad array of biological systems and processes. The book will be of interest to a wide audience of research scientists with an interest in the biophysical properties of lipids and the physiological consequences of their presence in biological systems, as well as graduate students, postdoctoral trainees, basic and clinical researchers, and pharmaceutical scientists. Specifically, the content will be relevant to researchers in the fields of biochemistry, molecular biophysics, pharmacology, neurobiology, cardiovascular biology, among others. Provides a comprehensive overview of the current knowledge of the interplay between cholesterol and PI(4,5) P2 Provides an overview of the emerging relationship between cholesterol and PI(4,5)P2 in biological systems and processes Discusses cellular processes and molecular mechanisms where lipid functions extend from parallel existence to crosstalk

With Cholesterol, Drs. Anna Bukiya and Alex Dopico have compiled a comprehensive resource on biological and clinical aspects of cholesterol, spanning biophysics and biochemistry, as well as the latest pharmacological discoveries employed to tackle disorders associated with abnormal cholesterol levels. Early chapters on basic biology offer guidance in cholesterol lab chemistry, cholesterol metabolism and synthesis, molecular evolution of cholesterol and sterols, cholesterol peptides, and cholesterol modulation. Chapters on cellular and organismal development discuss cholesterol transport in blood, lipoproteins, and cholesterol metabolism; cholesterol detection in the blood; cellular cholesterol levels; hypercholesterolemia; and the role of cholesterol in early human development. Pathophysical specialists consider familial hypobetalipoproteinemia, critical illness and cholesterol levels, coronary artery disease, CESD, cholesterol and viral pathology, cholesterol and neurodegenerative disorders, and cholesterol and substance use disorders. A final section examines pharmacology of drug delivery systems targeting cholesterol related disorders, cholesterol receptors, cholesterol reduction, statins, citrate lyase, cyclodextrins, and clinical management. Cholesterol: From Biophysics and Biochemistry to Pathology and Pharmacology empowers researchers, students, and clinicians across various disciplines to advance new cholesterol-based studies, improve clinical management, and drive drug discovery. Ties basic biology to clinical application and drug discovery Provides methods and protocols for lab-based cholesterol research and clinical testing Examines the latest pharmacological discoveries employed to tackle cholesterol related disorders Includes chapter contributions from a wide range of specialists, uniting various disciplines

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.

Advances in Cholesterol Research presents a range of topics which, for the most part, have not been reviewed in recent years in books published on cholesterol. The subject area can be divided into two main sections. The intracellular and extracellular dynamics of cholesterol. The intracellular dynamics of cholesterol includes the intracellular distributions of cholesterol, cellular functions of the sterol, cholesterol metabolism in steroidogenic tissues, the cholestryl ester cycle, relation between cholesterol and dolichol biosynthesis, and the role of cholesterol in tumor cell proliferation. The section on extracellular dynamics of cholesterol includes the biogenesis of high density lipoprotein subclasses, structure-function relation in lecithin: cholesterol acyltransferase, and the role of cholesterol in atherosclerosis and in membrane fusion.

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.