Chemical and Biophysical Approaches to Allosteric Modulation

• Published in: European journal of organic chemistry 2021-08, Vol.2021 (30), p.4245-4259
• Main Authors: Civera, Monica, Moroni, Elisabetta, Sorrentino, Luca, Vasile, Francesca, Sattin, Sara
• Format: Article
• Language: English
• Subjects: Allostery; Biological activity; Cell adhesion; Molecular dynamics; Native mass spectrometry; NMR spectroscopy; Proteins; Signal processing; Signal transduction; X-ray crystallography
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202100506

Allosteric regulation, i. e. the control exerted on an orthosteric site by an effector interacting at a distinct and distant site, represents a prime example of a precise tuning system of several key biological processes like gene transcription, cell adhesion and, most importantly, signal transduction. Since its discovery sixty years ago, the molecular mechanisms underlying this phenomenon have been extensively investigated. The aim of this minireview is to introduce the reader to the topic of protein allostery. In particular, we briefly overview the allosteric models postulated over the years and we describe the most relevant chemical and biophysical approaches reported so far for the identification of putative allosteric sites and/or for the investigation of allosteric signal propagation throughout the protein. An outlook of the main computational and experimental methods is followed by four case studies representative of different proteins classes: enzymes, hub proteins, cell receptors, and intrinsically disordered proteins. Since its discovery, allostery has emerged as a pivotal regulatory mechanism involved in many diverse biological processes. In this minireview, we present an overview of allostery models postulated through the years. In addition, we provide the description of useful computational and experimental approaches developed to study such a crucial process at the molecular level, followed by four representative case studies.