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SpringerLink Springer Biomedical and Life Sciences eBooks 2017 English+International

880-01 Preface; Contents; Introduction; 1 Arrestins: Discovery of the Family and Functional Role of Conformational Flexibility; Abstract; Brief History of Arrestins; The Functional Cycle of Arrestins; The Structural Evidence for Distinct Arrestin Conformations; Preferential Interaction of Signalling Proteins with Arrestins in Particular Conformations; Acknowledgements; References; 2 Overview of Arrestin Mediated Signaling with Receptors and Non-receptor Binding Partners; Abstract; References; Localization of Functional Elements on Arrestins.

5 Arrestin-3: The Structural Basis of Lower Receptor SelectivityAbstract; Introduction; Arrestin-3 Structure; Comparisons to the Rhodopsin-Arrestin-1 Complex; Acknowledgements; References; 6 Phosphate Sensor and Construction of Phosphorylation-Independent Arrestins; Abstract; Early Biochemistry and Structure-Function Characterization; Towards an Allosteric Model for Arrestin; Applications; References; 7 Comprehensive Analysis of the Role of Arrestin Residues in Receptor Binding; Abstract; Introduction: The Role of Arrestin in GPCR Trafficking and Signaling.

Membrane Interactions of Arrestin-1 and Binding StoichiometryPharmacological Relevance of Phosphobarcodes for Arrestin-Dependent Signaling; Acknowledgements; References; 8 How Arrestin Recognizes and Binds Active GPCRs; Abstract; The Pre-complex; Transition to the High-Affinity Complex; References; 9 Localization of Conformational Dynamics of Arrestins by HDX-MS; Abstract; What Can HDX-MS Reveal About Protein Conformation?; Introduction to Arrestin Structure; Arrestin Activation Mechanism Revealed by HDX-MS; Conformational Mechanism of Arrestin Selectivity Revealed by HDX-MS; Perspectives.

Molecular Mechanism of Arrestin-1 Engagement with Rhodopsin Revealed by Scanning MutagenesisScanning Mutagenesis as a Tool for GPCR Pharmacology Elucidation; Phosphorylation Defines the Nature of GPCR-Arrestin Interactions; Inactive Arrestin-1 and Its Key Regulation Sites; Pre-activation of Arrestin-1 by C-Tail Exchange Mechanism; Establishment of an Initial Phosphorylation-Dependent Binding; Activation and Phosphorylation States of the GPCR Influence the Conformation of the Final Complex; Active GPCR Recognition on a Single Residue Scale; GPCR Activation-Sensing Residues of Arrestin-1.

This volume summarizes our current understanding of the structural basis of the functions of arrestin family of proteins. Arrestins were first discovered as key players in the desensitization of G protein-coupled receptors (GPCRs). Recent studies showed that arrestins are important signal transducers in their own right, organizing multi-protein complexes and scaffolding numerous signaling cascades that regulate cell proliferation, differentiation, and apoptotic death. Here arrestin functions are described primarily from the structural prospective. The book covers basal structure of arrestin proteins, receptor binding-induced conformational changes in arrestins, as well as the structure of "pre-activated" mutants. Particular focus is on the arrestin elements interacting with numerous binding partners, GPCRs and cytoplasmic signaling proteins. We expect that this information and insights will help to understand and exploit the phenomenon of signaling bias, which is a new promising direction in drug discovery. The chapters are written by the world-class specialists in the field, mostly the people who actually contributed the data discussed. The book gives coherent historical prospective and describes the most recent findings. The book would be particularly useful for scientists in academia and industry working in the fields of pharmacology, cell biology, structural biology, and drug discovery. We expect that the focus on the molecular basis of protein-protein interactions would help to develop novel tools for engaging this important type of targets for research and therapeutic purposes.