Structural basis of μ-opioid receptor targeting by a nanobody antagonist.

The μ-opioid receptor (μOR), a prototypical G protein-coupled receptor (GPCR), is the target of opioid analgesics such as morphine and fentanyl. Due to the severe side effects of current opioid drugs, there is considerable interest in developing novel modulators of μOR function. Most GPCR ligands today are small molecules, however biologics, including antibodies and nanobodies, represent alternative therapeutics with clear advantages such as affinity and target selectivity.

Stepwise activation of a metabotropic glutamate receptor.

Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain that is linked via a cysteine-rich domain to their 7-transmembrane domain. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the extracellular ligand-binding domain to the G protein-coupling 7-transmembrane domain. In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5.

Structural Basis of μ-Opioid Receptor-Targeting by a Nanobody Antagonist.

The μ-opioid receptor (μOR), a prototypical member of the G protein-coupled receptor (GPCR) family, is the molecular target of opioid analgesics such as morphine and fentanyl. Due to the limitations and severe side effects of currently available opioid drugs, there is considerable interest in developing novel modulators of μOR function. Most GPCR ligands today are small molecules, however biologics, including antibodies and nanobodies, are emerging as alternative therapeutics with clear advantages such as affinity and target selectivity.

Who Serves Where: A Geospatial Analysis of Access to Endocrine Surgeons in the United States and Puerto Rico.

Background: The association between surgical volume and patient outcome is well established, with higher case volume associated with a lower risk of complications. We hypothesized that the geographic distribution of endocrine/head and neck surgeons with an endocrine focus in the United States and Puerto Rico may limit access to many potential patients, particularly in rural areas.

Methods: We used web-based directories from the American Association of Endocrine Surgeons, American Head and Neck Society, and the American Academy of Otolaryngology-Head and Neck Surgery to identify endocrine surgery specialists in the United States and Puerto Rico.