Direct Mechanisms In 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.

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

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

Impacts that threaten or indeed compromise the integrity of tissues trigger the development of a defence response, which through the activity of the nociceptive system includes pain. If the noxious impact does not induce tissue damage, the pain, called “nociceptive” pain, ceases within seconds after the impact is withdrawn. In contrast, if tissue damage does occur, a pain experience that usually persists until the injury is resolved and includes two major pathological sensory experiences, hypersensitivity to heat stimuli (i.e. heat hyperalgesia) and/or hypersensitivity to mechanical stimuli (i.e. mechanical allodynia) develop. The cellular and molecular mechanisms underlying the development of nociceptive pain are fairly well understood. Our understanding of the development of pain associated with tissue injury has also significantly improved in the last decades. Hence, two fundamental mechanisms, interactions between the nervous and immune systems both within and without the central nervous system and sensitization that is a use-dependent increase in the sensitivity and activity of neurons involved in nociceptive processing have been identified being pivotal for the development of tissue injury-associated pain. However, important details of the cellular and molecular mechanisms, which account for the development of the pathological sensory experiences and those experiences becoming persistent, still await elucidation.

The Membranes of Cells, Third Edition, provides a basic guide to biomembranes, connecting researchers to the numerous fields of biology. The new edition offers a complete update of content based on new understandings in the field. Foundational content for graduate students, researchers, professors, and undergraduate students across the sciences is provided, succinctly covering all of the basic information needed for lipids and membranes. Connects membrane research to numerous fields of biology Provides a basic guide to the interdisciplinary studies of membranes Offers a companion website with recommended readings and dynamic visual representations of the content Includes four color illustrations to offer the best visual representation of concepts

Biological membranes provide the fundamental structure of cells and viruses. Because much of what happens in a cell or in a virus occurs on, in, or across biological membranes, the study of membranes has rapidly permeated the fields of biology, pharmaceutical chemistry, and materials science. The Structure of Biological Membranes, Third Edition pro

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.