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.

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.

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.

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

This volume brings together information on membrane organization and dynamics from a variety of spectroscopic, microscopic and simulation approaches, spanning a broad range of time scales. The implication of such dynamic information on membrane function in health and disease is a topic of contemporary interest. The chapters cover various aspects of membrane lipid and protein dynamics, explored using a battery of experimental and theoretical approaches. The synthesis of information and knowledge gained by utilizing multiple approaches will provide the reader with a comprehensive understanding of the underlying membrane dynamics and function, which will help to develop robust dynamic models for the understanding of membrane function in healthy and diseased states. In the last few years, crystal structures of an impressive number of membrane proteins have been reported, thanks to tremendous advances in membrane protein crystallization techniques. Some of these recently solved structures belong to the G protein-coupled receptor (GPCR) family, which are particularly difficult to crystallize due to their intrinsic flexibility. Nonetheless, these static structures do not provide the necessary information to understand the function of membrane proteins in the complex membrane milieu. This volume will address the dynamic nature of membrane proteins within the membrane and will provide the reader with an up-to date overview of the theory and practical approaches that can be used. This volume will be invaluable to researchers working in a wide range of scientific areas, from biochemistry and molecular biology to biophysics and protein science. Students of these fields will also find this volume very useful. This book will also be of great use to those who are interested in the dynamic nature of biological processes.

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

Covering theoretical methods and computational techniques in biomolecular research, this book focuses on approaches for the treatment of macromolecules, including proteins, nucleic acids, and bilayer membranes. It uses concepts in free energy calculations, conformational analysis, reaction rates, and transition pathways to calculate and interpret b