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Of 12 serology assays tested, four detect antibodies in more than 80% of patients with COVID-19.

Stabilization of an active and inactive conformation of the β₂-adrenergic receptor by allosteric nanobodies reveals differential ligand-dependent regulation of receptor states to control G-protein-coupled receptor activation.

Cryo-electron microscopy structures of the thyrotropin receptor reveal the basis for the activation of the receptor by autoantibodies in patients with Graves’ disease.

It is unknown how GPR161, an orphan receptor involved in Hedgehog signaling, is activated. This study identifies a sterol that promotes GPR161-driven cAMP signaling but shows that cAMP is dispensable for Hedgehog pathway repression.

Use of the consensus protein design method facilitated the generation of stable engineered mammalian odorant receptors to gain insight into the molecular properties of odorant–receptor interactions.

Here, Zhang et al. explore fusion protein strategies to facilitate cryo-EM structural studies of GPCRs alone- without signal transducers- in ligand bound or unliganded form.

A cryo-electron structure of the µ-opioid receptor in complex with the peptide agonist DAMGO and the inhibitory G protein G_i reveals structural determinants of its G protein-binding specificity.

Through the use of cryo-electron microscopy and molecular dynamics stimulations, mechanistic insight into the binding of an odorant to the human odorant receptor OR51E2 is provided.

X-ray crystallography and molecular dynamics simulations of the μ-opioid receptor reveal the conformational changes in the extracellular and intracellular domains of this G-protein-coupled receptor that are associated with its activation.

Determination of the cryo-EM structures of active neurokinin-1 receptor bound to substance P or the G_q biased peptide SP6–11 reveals that interactions with the receptor extracellular loops regulate G protein signaling selectivity.

Structures of the iron transporter ferroportin and the peptide hormone hepcidin suggest how iron homeostasis is tightly regulated.

Computational docking to the the μ-opioid-receptor identifies PZM21, a novel selective biased agonist that generates substantial affective analgesia in mice without altering respiration or inducing drug reinforcement.

The X-ray crystal structure of the mouse δ-opioid receptor in complex with the subtype-selective antagonist naltrindole is reported.

The crystal structure of active mouse SMO in complex with the SAG21k agonist and a stabilizing intracellular binding nanobody reveals the structural basis of SMO regulation by PTCH1.

The µ-opioid receptor is a key clinical target. Here, the authors describe nanobody NbE, a selective and high affinity antagonist, which is downsized to small cyclic peptides. The work enables unique receptor targeting based on nanobody interaction.

The crystal structure of β-arrestin-1 in complex with a fully phosphorylated 29-amino-acid carboxy-terminal peptide derived from the V2 vasopressin receptor is reported; the structure of the complex shows striking conformational differences in β-arrestin-1 when compared with its inactive conformation.

The ability to design functional sequences is central to protein engineering and biotherapeutics. Here the authors introduce a deep generative alignment-free model for sequence design applied to highly variable regions and design and test a diverse nanobody library with improved properties for selection experiments.

Here, by developing a high-affinity camelid antibody fragment that stabilizes the active state of the β₂-adrenoceptor, the X-ray crystal structures of the receptor in complex with three agonists, including adrenaline, were determined.

The crystal structure of the mouse μ-opioid receptor bound to an antagonist is described, with possible implications for the future development of analgesics.

Yeast surface display platform allows nanobody discovery within two to three weeks. Examples include nanobodies for crystallographic applications, targeting nonpurified antigen or conformationally selective nanobodies to two distinct human GPCRs.

Very little is known about how a G-protein-coupled receptor (GPCR) transitions from an inactive to an active state, but this study has solved the X-ray crystal structures of the human M2 muscarinic acetylcholine receptor bound to a high-affinity agonist in an active state and to a high-affinity agonist and a small-molecule allosteric modulator in an active state; the structures provide insights into the activation mechanism and allosteric modulation of muscarinic receptors.

The determination of high resolution structures of G protein coupled receptors (GPCRs) in complex with heterotrimeric G proteins is challenging. Here authors develop an antibody fragment, mAB16, which stabilizes GPCR/G-protein complexes and facilitates the application of high resolution cryo-EM.

A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and potency.

NMR spectroscopy reveals the conformational changes of the μ-opioid receptor that are associated with receptor activation, helping to explain why the allosteric coupling between the agonist-binding pocket and the cytoplasmic G-protein-coupling interface of this receptor is relatively weak.

Here, pharmacological and biochemical evidence is provided that shows that G-protein coupling to the β₂-adrenergic receptor stabilizes a ‘closed’ conformation of the G-protein-coupled receptor (GPCR) and that that the effects of the G protein on the ligand-binding site of the GPCR are observed even in the absence of a bound agonist.

The X-ray crystal structures of the human σ1 receptor bound to two different ligands are reported, revealing the overall architecture, oligomerization state, and molecular basis for ligand recognition by this protein.

A FACS aided selection process combined with characterization of the selected clones facilitates phage display screening to obtain antibodies against a given target from libraries.