Intrinsically Disordered Proteins

In this brief, Vladimir Uversky discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). Beginning with an introduction to the concept of protein intrinsic disorder, Uversky then goes on to describe the peculiar amino acid sequences of IDPs, their structural heterogeneity, typical functions and disorder-based binding modes. In the final sections, Uversky discusses IDPs in human diseases and as potential drug targets. This volume provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.

The edition details methods to study intrinsically disordered proteins (IDPs) including recent topics such as extremely high-affinity disordered complexes, kinetics that evade established concepts, liquid-liquid phase separation, and novel disorder-driven allosteric mechanisms. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Intrinsically Disordered Proteins: Methods and Protocols aims to help scientists with different backgrounds to further their investigations into these fascinating and dynamic molecules. Chapter 24 is available open access under a CC BY 4.0 license via link.springer.com. Chapters “40 and 42 ” are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This book discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). The properties of IDPs and IDPRs are highly complementary to those deriving from the presence of a unique and well-defined three-dimensional fold. Ignored for a long time in high-resolution studies of proteins, intrinsic protein disorder is now recognized as one of the key features for a large variety of cellular functions, where structural flexibility presents a functional advantage in terms of binding plasticity and promiscuity and this volume explores this exciting new research. Recent progress in the field has radically changed our perspective to study IDPs through NMR: increasingly complex IDPs can now be characterized, a wide range of observables can be determined reporting on the structural and dynamic properties, computational methods to describe the structure and dynamics are in continuous development and IDPs can be studied in environments as complex as whole cells. This volume communicates the new exciting possibilities offered by NMR and presents open questions to foster further developments. Intrinsically Disordered Proteins Studied by NMR Spectroscopy provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.

Intrinsically Disordered Proteins: Dynamics, Binding, and Function thoroughly examines and ties together the fundamental biochemical functions of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs), including signaling, binding, and regulation, with the methodology for study and the associated pathways for drug design and therapeutic intervention. The role of new mechanistic, computational, and experimental approaches in IDP study are explored in depth, with methods for the characterization of IDP dynamics; models, simulations, and mechanisms of IDP and IDR binding; and biological and medical implications of IDP dynamics prominently featured. Written and edited by leading scientists in the field, this book explores groundbreaking areas such as ensemble descriptions of IDPs and IDRs, single-molecule studies of IDPs and IDRs, IDPs and IDRs in membraneless organelles, and molecular mechanisms of fibrillation of IDPs. Intrinsically Disordered Proteins provides students and researchers in biochemistry, molecular biology, and applied microbiology with a comprehensive and updated discussion of the complex dynamics of IDPs and IDRs. Provides in-depth discussion of fundamental IDP and IDR dynamics, function, and binding, with mechanistic insight to support new drug development Describes the role of new computational and experimental approaches in characterizing the binding of IDPs to their functional targets Features chapter contributions from international experts in IDP and IDR biochemical function and methods of study

The existence and functioning of intrinsically disordered proteins (IDPs) challenge the classical structure-function paradigm that equates function with a well-defined 3D structure. Uncovering the disordered complement of proteomes and understanding their functioning can extend the structure-function paradigm to herald new breakthroughs in drug dev

Instrumental techniques for analyzing intrinsically disordered proteins The recently recognized phenomenon of protein intrinsic disorder is gaining significant interest among researchers, especially as the number of proteins and protein domains that have been shown to be intrinsically disordered rapidly grows. The first reference to tackle this little-documented area, Instrumental Analysis of Intrinsically Disordered Proteins: Assessing Structure and Conformation provides researchers with a much-needed, comprehensive summary of recent achievements in the methods for structural characterization of intrinsically disordered proteins (IDPs). Chapters discuss: Assessment of IDPs in the living cell Spectroscopic techniques for the analysis of IDPs, including NMR and EPR spectroscopies, FTIR, circular dichroism, fluorescence spectroscopy, vibrational methods, and single-molecule analysis Single-molecule techniques applied to the study of IDPs Assessment of IDP size and shape Tools for the analysis of IDP conformational stability Mass spectrometry Approaches for expression and purification of IDPs With contributions from an international selection of leading researchers, Instrumental Analysis of Intrinsically Disordered Proteins: Assessing Structure and Conformation fills an important need in a rapidly growing field. It is required reading for biochemists, biophysicists, molecular biologists, geneticists, cell biologists, physiologists, and specialists in drug design and development, proteomics, and molecular medicine with an interest in proteins and peptides.

Over the past decade, there has been an explosive development of research of intrinsically disordered proteins (IDPs), which are also known as unfolded proteins. Structural biologists now recognize that the functional diversity provided by disordered regions complements the functional repertoire of ordered protein regions. In Intrinsically Disordered Protein Analysis :Methods and Experimental Tools, expert researchers explore the high abundance of IDPs in various organisms, their unique structural features, numerous functions, and crucial associations with different diseases. Volume 1 includes sections on assessing IDPs in the living cell,NMR based techniques, vibrational spectroscopy, and other spectroscopic techniques. Written in the highly successful Methods in Molecular BiologyTM series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, Intrinsically Disordered Protein Analysis: Methods and Experimental Tools helps scientists further their investigations of these fascinating and dynamic molecules.

Detailed characterization of fuzzy interactions will be of central importance for understanding the diverse biological functions of intrinsically disordered proteins in complex eukaryotic signaling networks. In this volume, Peter Tompa and Monika Fuxreiter have assembled a series of papers that address the issue of fuzziness in molecular interactions. These papers provide a broad overview of the phenomenon of fuzziness and provide compelling examples of the central role played by fuzzy interactions in regulation of cellular signaling processes and in viral infectivity. These contributions summarize the current state of knowledge in this new field and will undoubtedly stimulate future research that will further advance our understanding of fuzziness and its role in biomolecular interactions.