Crystal structures of the M1 and M4 muscarinic acetylcholine receptors.
Nature 531(7594):335 (2016)
Muscarinic M1-M5 acetylcholine receptors are G-protein-coupled receptors that regulate many vital functions of the central and peripheral nervous systems. In particular, the M1 and M4 receptor subtypes have emerged as attractive drug targets for treatments of neurological disorders, such as Alzh...
Structural Insights into the Dynamic Process of β2-Adrenergic Receptor Signaling.
Cell 161(5):1101 (2015)
G-protein-coupled receptors (GPCRs) transduce signals from the extracellular environment to intracellular proteins. To gain structural insight into the regulation of receptor cytoplasmic conformations by extracellular ligands during signaling, we examine the structural dynamics of the cytoplasmi...
The dynamic process of β(2)-adrenergic receptor activation.
Cell 152(3):532 (2013)
G-protein-coupled receptors (GPCRs) can modulate diverse signaling pathways, often in a ligand-specific manner. The full range of functionally relevant GPCR conformations is poorly understood. Here, we use NMR spectroscopy to characterize the conformational dynamics of the transmembrane core of ...
Structure of the δ-opioid receptor bound to naltrindole.
Nature 485(7398):400 (2012)
The opioid receptor family comprises three members, the µ-, δ- and κ-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excel...
Crystal structure of the µ-opioid receptor bound to a morphinan antagonist.
Nature 485(7398):321 (2012)
Opium is one of the world's oldest drugs, and its derivatives morphine and codeine are among the most used clinical drugs to relieve severe pain. These prototypical opioids produce analgesia as well as many undesirable side effects (sedation, apnoea and dependence) by binding to and activating t...
Crystal structure of the β2 adrenergic receptor-Gs protein complex.
Nature 477(7366):549 (2011)
G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-oc...
Structure of a nanobody-stabilized active state of the β(2) adrenoceptor.
Nature 469(7329):175 (2011)
G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due...
Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor.
Nature 463(7277):108 (2010)
G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters. They are the largest group of therapeutic targets for a broad spectrum of diseases. Recent crystal structures of GPCRs have revealed structural conservatio...
GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function.
Science 318(5854):1266 (2007)
The beta2-adrenergic receptor (beta2AR) is a well-studied prototype for heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) that respond to diffusible hormones and neurotransmitters. To overcome the structural flexibility of the beta2AR and to facilitate its c...
High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor.
Science 318(5854):1258 (2007)
Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors constitute the largest family of eukaryotic signal transduction proteins that communicate across the membrane. We report the crystal structure of a human beta2-adrenergic receptor-T4 lysozyme fusion protein bound to ...
Crystal structure of the human beta2 adrenergic G-protein-coupled receptor.
Nature 450(7168):383 (2007)
Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and neurotransmitters has been hindered by their low natural abundance, inherent structural flexibility, and instability in detergent solutions. Here we report a structure of the human beta2 adrenoceptor (beta2AR), which was...
A monoclonal antibody for G protein-coupled receptor crystallography.
Nature Methods 4(11):927 (2007)
G protein-coupled receptors (GPCRs) constitute the largest family of signaling proteins in mammals, mediating responses to hormones, neurotransmitters, and senses of sight, smell and taste. Mechanistic insight into GPCR signal transduction is limited by a paucity of high-resolution structural in...
Probing the beta2 adrenoceptor binding site with catechol reveals differences in binding and activation by agonists and partial agonists.
Journal of Biological Chemistry 280(23):22165 (2005)
The beta(2) adrenergic receptor (beta(2)AR) is a prototypical family A G protein-coupled receptor (GPCR) and an excellent model system for studying the mechanism of GPCR activation. The beta(2)AR agonist binding site is well characterized, and there is a wealth of structurally related ligands wi...