Structural basis for partial agonism in 5-HT receptors.

Hyperactivity of serotonin 3 receptors (5-HTR) underlies pathologies associated with irritable bowel syndrome and chemotherapy-induced nausea and vomiting. Setrons, a class of high-affinity competitive antagonists, are used in the treatment of these conditions. Although generally effective for chemotherapy-induced nausea and vomiting, the use of setrons for treating irritable bowel syndrome has been impaired by adverse side effects.

Prediction of an Upper Limit for the Fraction of Interprotein Cross-Links in Large-Scale In Vivo Cross-Linking Studies.

Chemical cross-linking and mass spectrometry is of growing use for establishment of distance constraints on protein conformations and interactions. Whereas intraprotein cross-links can arise from proteins in isolation, interprotein cross-links reflect proximity of two interacting proteins in the sample. Prediction of expected ratios of the number of interprotein to intraprotein cross-links is hindered by lacking comprehensive knowledge on the interactome network and global occupancy levels for all interacting complex subunits.