G-Protein-Coupled Receptors: from Structural Insights to Functional Mechanisms G-Protein-Coupled Receptors: from Structural Insights to Functional Mechanisms A Biochemical Society Focused Meeting co-organized with Monash University held at Monash University Prato Centre, Prato, Italy, 12–14 September 2012. Organized and Edited by Bice Chini (CNR Institute of Neuroscience, Italy), Marco Parenti (University of Milano–Bicocca, Italy), David Poyner (Aston University, U.K.) and Mark Wheatley (University of Birmingham, U.K.) G-Protein-Coupled Receptors: from Structural Insights to Functional Mechanisms Bice Chini*, Marco Parenti†, David R. Poyner‡ 1 and Mark Wheatley§ *CNR Institute of Neuroscience, via Vanvitelli 32, Milan, 20129, Italy, †Faculty of Medicine University of Milan-Bicocca Via Cadore 48, 20900 Monza, Italy, ‡School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, U.K., and §School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K. Abstract The papers resulting from the recent Biochemical Society Focused Meeting ‘G-Protein-Coupled Receptors: from Structural Insights to Functional Mechanisms’ held in Prato in September 2012 are introduced in the present overview. A number of future goals for GPCR (G-protein-coupled receptor) research are considered, including the need to develop biophysical and computational methods to explore the full range of GPCR conformations and their dynamics, the need to develop methods to take this into account for drug discovery and the importance of relating observations on isolated receptors or receptors expressed in model systems to receptor function in vivo. The Biochemical Society/Monash University Focused Meet- ing ‘G-Protein-Coupled Receptors: from Structural Insights to Functional Mechanisms’ held in Prato in September 2012 has proved particularly timely. During the course of the meeting, preliminary data for two new GPCR (G-protein- coupled receptor) structures were revealed, including the very first family B GPCR crystal structure. During the preparation of this issue of Biochemical Society Transactions, it was announced that the 2012 Nobel Prize for Chemistry had been awarded to Dr Robert Lefkowitz and Dr Brian Kobilka for their outstanding contributions to the biology of GPCRs; many of their close collaborators were speakers at the meeting. Organizing a meeting at such a pivotal time was a real privilege, as was editing this collection of papers arising from the event. Given the current ferment of excitement about GPCR structure, it is not surprising that a number of papers in this Key words: β-arrestin, crystal structure, G-protein-coupled receptor (GPCR), modelling, pharmacology. Abbreviations used: GPCR, G-protein-coupled receptor. 1 To whom correspondence should be addressed (email D.R.Poyner@aston.ac.uk). collection focus directly on crystallization. Fiona Marshall [1] presents an overview of crystallization strategies, and Tony Warne [2] summarizes what is currently known about how agonists binding to the β -receptor cause the changes necessary for G-protein activation. The dynamics of β - receptor activation have previously been probed by FRET (fluorescence resonance energy transfer) by Kobilka and co-workers [3]; Jean-Louis Ban` eres [4] describes his recent study extending the technique to look at the conformational landscape of the ghrelin receptor. The information available from family A GPCRs is also being applied to family B GPCRs. Lawrence Miller [5] describes his studies to determine how secretin binds to its receptor and Barwell et al. [6] consider how the CGRP (calcitonin gene-related peptide) receptor may become activated upon agonist binding. Inna Hoyer’s paper [7] describes the mapping of an allosteric binding site at the TSH (thyroid-stimulating hormone) receptor. Although structural studies have recently dominated the GPCR field, there are many other aspects to their role, and these were also explored at the meeting. GPCR Biochem. Soc. Trans. (2013) 41, 135–136; doi:10.1042/BST20120344 C  The Authors Journal compilation C  2013 Biochemical Society 135