Membrane Transporters

Transporters and channels are membrane proteins that mediate the traffic of metabolites, water and ions across biological membranes. Membrane transport proteins are crucial to maintain homeostasis and assure cell survival upon intracellular or environmental stress. A failure of any of these transport systems may have dramatic consequences for cell function. There is increasing evidence that membrane transport proteins play important functions in healthy conditions and that their absence or dysfunction may cause diseases. In recent years much attention has been paid to diseases resulting from defective transporters (“carrier diseases”) and ion channels (“channelopathies”). Very interestingly, altered expression of transporters has been described in several human pathologies. On this basis, many transport proteins are well acknowledged targets for drugs. Many others are involved in drug delivery and disposition and/or are considered potential targets. Others are off-targets for drugs and then, are responsible for side effects. Thus, membrane protein drug discovery is now an emerging field where the search for physiological mechanisms of regulation and for chemical compounds as modulators of transport activity, present new opportunities for drug development and for new therapies. This Research Topic addresses the latest research advances in membrane transport proteins, stimulating future research on these important protein families.

This book provides a molecular view of membrane transport by means of numerous biochemical and biophysical techniques. The rapidly growing numbers of atomic structures of transporters in different conformations and the constant progress in bioinformatics have recently added deeper insights. The unifying mechanism of energized solute transport across membranes is assumed to consist of the conformational cycling of a carrier protein to provide access to substrate binding sites from either side of a cellular membrane. Due to the central role of active membrane transport there is considerable interest in deciphering the principles of one of the most fundamental processes in nature: the alternating access mechanism. This book brings together particularly significant structure-function studies on a variety of carrier systems from different transporter families: Glutamate symporters, LeuT-like fold transporters, MFS transporters and SMR (RND) exporters, as well as ABC-type importers. The selected examples impressively demonstrate how the combination of functional analysis, crystallography, investigation of dynamics and computational studies has made it possible to create a conclusive picture or more precisely, “a molecular movie”. Although we are still far from a complete molecular description of the alternating access mechanism, remarkable progress has been made from static snapshots towards membrane transport dynamics.

An introduction to the principles of membrane transport: How molecules and ions move across the cell membrane by simple diffusion and by making use of specialized membrane components (channels, carriers, and pumps). The text emphasizes the quantitative aspects of such movement and its interpretation in terms of transport kinetics. Molecular studies of channels, carriers, and pumps are described in detail as well as structural principles and the fundamental similarities between the various transporters and their evolutionary interrelationships. The regulation of transporters and their role in health and disease are also considered. Provides an introduction to the properties of transport proteins: channels, carriers, and pumps Presents up-to-date information on the structure of transport proteins and on their function and regulation Includes introductions to transport kinetics and to the cloning of genes that code transport proteins Furnishes a link between the experimental basis of the subject and theoretical model building

This book provides an up-to-date overview of the architecture and biosynthesis of bacterial and archaeal cell walls, highlighting the evolution-based similarities in, but also the intriguing differences between the cell walls of Gram-negative bacteria, the Firmicutes and Actinobacteria, and the Archaea. The recent major advances in this field, which have brought to light many new structural and functional details, are presented and discussed. Over the past five years, a number of novel systems, e.g. for lipid, porin and lipopolysaccharide biosynthesis have been described. In addition, new structural achievements with periplasmic chaperones have been made, all of which have revealed amazing details on how bacterial cell walls are synthesized. These findings provide an essential basis for future research, e.g. the development of new antibiotics. The book’s content is the logical continuation of Volume 84 of SCBI (on Prokaryotic Cytoskeletons), and sets the stage for upcoming volumes on Protein Complexes.

Studies of membrane transporters have had great impact on our und- standing human diseases and the design of effective drugs. About 30% of current clinically marketed drugs are targeting membrane transporters or channels. Membrane Transporters: Methods and Protocols provides various practical methodologies for the ongoing research on membrane transporters. To provide readers the most up-to-date information, several emerging fields and methodologies are embraced in this book, including pharmacogenomics, bioin-formatics, and microarray technology. Pharmacogenomics studies of membrane transporters are useful in drug discovery and in predicting drug responses in the clinic. In this volume, the current status of pharma- genomics studies of transporters is reviewed and research methodologies in this field are described. Transporter classification is important in studying the structure and function of membrane transporters and has thus triggered intensive interest in recent years. Membrane Transporters: Methods and Protocols provides a systematic classification of all transmembrane transport proteins found in living org- isms on Earth. This classification system will be helpful for further studies on various aspects of membrane transporters, especially for such large-scale gene expression studies as those employing microarray technologies. Bioinformatics is frequently used in transporter studies and has become indispensable for all kinds of research methods. Commonly used bio- formatics methods, such as databases and tools for sequence analysis and - tif studies, are explained in order to facilitate membrane transporters research. Because of heterogeneous sources and tremendous amounts of data, data in- gration has become one of the most important issues in transporter studies.

Transport and Diffusion across Cell Membranes is a comprehensive treatment of the transport and diffusion of molecules and ions across cell membranes. This book shows that the same kinetic equations (with appropriate modification) can describe all the specialized membrane transport systems: the pores, the carriers, and the two classes of pumps. The kinetic formalism is developed step by step and the features that make a system effective in carrying out its biological role are highlighted. This book is organized into six chapters and begins with an introduction to the structure and dynamics of cell membranes, followed by a discussion on how the membrane acts as a barrier to the transmembrane diffusion of molecules and ions. The following chapters focus on the role of the membrane's protein components in facilitating transmembrane diffusion of specific molecules and ions, measurements of diffusion through pores and the kinetics of diffusion, and the structure of such pores and their biological regulation. This book methodically introduces the reader to the carriers of cell membranes, the kinetics of facilitated diffusion, and cotransport systems. The primary active transport systems are considered, emphasizing the pumping of an ion (sodium, potassium, calcium, or proton) against its electrochemical gradient during the coupled progress of a chemical reaction while a conformational change of the pump enzyme takes place. This book is of interest to advanced undergraduate students, as well as to graduate students and researchers in biochemistry, physiology, pharmacology, and biophysics.

With a detailed analysis of the mass transport through membrane layers and its effect on different separation processes, this book provides a comprehensive look at the theoretical and practical aspects of membrane transport properties and functions. Basic equations for every membrane are provided to predict the mass transfer rate, the concentration distribution, the convective velocity, the separation efficiency, and the effect of chemical or biochemical reaction taking into account the heterogeneity of the membrane layer to help better understand the mechanisms of the separation processes. The reader will be able to describe membrane separation processes and the membrane reactors as well as choose the most suitable membrane structure for separation and for membrane reactor. Containing detailed discussion of the latest results in transport processes and separation processes, this book is essential for chemistry students and practitioners of chemical engineering and process engineering. Detailed survey of the theoretical and practical aspects of every membrane process with specific equations Practical examples discussed in detail with clear steps Will assist in planning and preparation of more efficient membrane structure separation