Single-molecule measurement of conformational dynamics using a genetically encoded fluorescent probe suggests that the selectivity filter region of TRPV1 channels undergoes dynamic motion during agonist activation.
Structure-based virtual screening reveals multiple novel TRPV5 inhibitors that bind and exert their effect from previously unidentified binding sites as characterized by cryo-electron microscopy and electrophysiology.
Pro-nociceptive and pro-inflammatory TRPM3 (transient receptor potential melastatin 3) channels, expressed in somatosensory neurons, are inhibited by activation of Gαi-coupled receptors, such as µ-opioid receptors, in vitro and in vivo.
Disease-associated mutants of the TRPM3 ion channel are overactive, and they are inhibited by the antiepileptic medication primidone, offering a potential therapeutic intervention to treat this channelopathy.
Novel capsaicin analogs with conserved chemistry but varying sizes were used as molecular rulers to investigate energetics of conformational changes in the ligand-binding pocket and mechanisms of TRPV1 ligand-gating.