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G-protein-coupled-receptors: from structural insights to functional mechanisms - co-organized by the Biochemical Society and Monash University

12—14 September 2012

Monash University Prato Centre, Italy

Meeting background

G-protein-coupled receptors (GPCRs) are the subject of intense research effort, both in academic laboratories and within the pharmaceutical industry. There have been a series of very exciting advances in the field recently, including the publication of several GPCR crystal structures representing ground state and active states. This new structural insight increases our understanding of functional receptor mechanisms as well as the potential for therapeutic intervention and has had an impact throughout the GPCR field as a whole. In addition to crystallography, which presents a static ‘snap-shot’ of these very dynamic proteins, the synergistic approaches of biophysics, molecular modelling, protein chemistry, pharmacology and cell biology are helping to address key receptor functions including ligand binding, receptor activation, coupling to effectors and resultant signalling mechanisms and receptor trafficking. This two day meeting, based at Prato, near Florence in Italy, will examine GPCRs from Families A and B, thereby revealing the extent of shared mechanisms for ligand binding and activation but also highlighting points of diversity.

David Poyner (Aston University, United Kingdom)
Mark Wheatley (University of Birmingham, United Kingdom)
Bice Chini (CNR Institute of Neuroscience, Italy)
Marco Parenti (University of Milano-Bicocca, Italy)
Wednesday 12 September 2012
16:30 - 17:30 Registration with welcome drinks reception

Thursday 13 September 2012
08:50 - 09:00
The Organizers
09:00 - 09:40
Arresting inflammation: Contributions of plasma membrane and endosomal signaling to neuropeptide-driven inflammatory disease
Nigel Bunnett (Monash University, Australia)
09:40 - 10:20
Regulation of GABAB receptors by auxiliary subunits
Bernhard Bettler (University of Basel, Switzerland)
10:20 - 11:00
How ligands, signaling proteins and dimerization affect ghrelin receptor conformational landscape
Jean-Louis Banères (University of Montpellier, France)
11:00 - 11:30 Coffee/tea break

11:30 - 11:45
Structural investigation of GPCR transmembrane signaling by use of Nanobodies
Selected oral communication - Jan Steyaert (VUB, Belgium)
11:45 - 12:00
Single-molecule analysis of G Protein-Coupled Receptors localization and clustering on the cell membrane using the photo-activated localization microscopy (PALM)
Selected oral communication - Marco Scarselli (University of Pisa, Italy)
12:00 - 12:15
Natural peptide libraries as pharmacological tools to study GPCR signaling
Selected oral communication - Christian Gruber (Medical University of Vienna, Austria)
12:15 - 12:30
The impact of endogenous allosteric binders on Adenosine A2A receptor structure and function
Selected oral communication - Hugo Gutierrez de Teran (Public Galician Foundation of Genomic Medicine, Spain)
12:30 - 12:45
Switching agonism to antagonism and vice versa by molecular sampling the allosteric binding pocket of the TSH receptor
Selected oral communication - Inna Hoyer (Leibniz-Institut fuer Molekulare Pharmakologie, Germany)
12:45 - 13:00
Identification of bitopic and allosteric ligands targeting the dopamine D2 receptor
Selected oral communication - Jeremy Shonberg (Monash University, Australia)
13:00 - 13:15
Endomorphin-2 is an arrestin-biased agonist because it induces greater MOPr phosphorylation than predicted from its efficacy for G protein coupling
Selected oral communication - Eamonn Kelly (University of Bristol, United Kingdom)
13:15 - 14:15 Lunch with Poster Session (Even numbers only)

14:15 - 14:55
Fluorescent ligands to investigate GPCR binding properties and oligomerization
Thierry Durroux (CNRS Montpellier, France)
14:55 - 15:35
Immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in GPCRs : The OX1 receptor case and beyond
Thierry Voisin (INSERM U773, France)
15:35 - 16:15
The orthosteric agonist binding pocket in the prototypic class B G protein-coupled secretin receptor
Laurence Miller (Mayo Clinic, U.S.A.)
16:15 - 16:55
Allosteric regulation of GPCRs by G proteins: insights from the crystal structure of a GPCR-G protein complex
Roger Sunahara (University of Michigan, U.S.A.)
16:55 - 18:00 Poster Session (Even numbers only) with drinks reception

19:00 Conference dinner

Friday 14 September 2012
08:45 - 09:25
Structural correlates of ligand activity in β-adrenoceptors
Tony Warne (MRC, United Kingdom)
09:25 - 10:05
Functional selectivity of human oxytocin receptor: biological roles and pharmacological modulation
Bice Chini (CNR, Italy)
10:05 - 10:45
Understanding allosteric drug action and signal bias at the glucagon-like peptide-1 (GLP1) receptor
Patrick Sexton (Monash University, Australia)
10:45 - 11:15 Coffee/tea break

11:15 - 11:30
Development of simple chemiluminescent assay formats to measure GPCR trafficking on benchtop instruments
Selected oral communication - Mike Brown (DiscoveRx, United Kingdom)
11:30 - 11:45
Differential endosomal sorting of a novel P2Y12 purinoreceptor mutant identified in a patient with a mild bleeding disorder
Selected oral communication - Margaret Cunningham (University of Bristol, United Kingdom)
11:45 - 12:00
D6 is a β-arrestin-biased signalling chemokine scavenger receptor
Selected oral communication - Elena Monica Borroni (Istituto Clinico Humanitas, Italy)
12:00 - 14:00 Lunch with Poster Session (Odd numbers only)

14:00 - 14:40
Delineating the complexity of biased and full agonism reveals the existence of a new distinct active AT1 receptor entity: toward a redefinition of “biased agonist”
Céline Gales (Inserm/UPS UMR 1048 - I2MC, France)
14:40 - 15:20
Ligand binding and activation of the CGRP receptor; a novel family B GPCR
David Poyner (Aston University, United Kingdom)
15:20 - 16:00
A new generation of orexin receptor antagonists discovered using structure based drug design
Fiona Marshall (Heptares Therapeutics, United Kingdom)
16:00 - 16:40
Small becomes big in GPCR ligand discovery
Rob Leurs (Vrije Universiteit Amsterdam, Netherlands)
16:40 Closing remarks and close of conference