Structure and Function of Intrinsically Disordered Proteins

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 development. Structure and Function of Intrinsically Disordered Proteins thoroughly covers the history up to the latest developments in this field.

After examining the principles of protein structure, the classical paradigm, and the history of structural disorder, the book focuses on physical techniques for the identification and characterization of IDPs. It discusses proteomic and bioinformatic approaches and shows how IDPs behave under crowding conditions in living cells. The next several chapters describe the structure, correlating biological processes, and molecular mechanisms of IDPs. The author also explores the evolutionary advancement of structural disorder in proteomes and possible ways of extending the structure-function paradigm to encompass both ordered and disordered states of proteins. He concludes with discussions on the involvement of IDPs in various diseases and how to establish rational drug design through detailed characterization of IDPs.

Although drug discovery rates have leveled off, new insight generated by the study of IDPs may offer fresh strategies for drug development. This work illustrates how these proteins defy the structure-function paradigm and play important regulatory and signaling roles.

Peter Tompa is Group Leader in the Laboratory of Intrinsically Disordered Proteins, Institute of Enzymology, Biological Research Center at the Hungarian Academy of Sciences in Budapest.