Serotonin 2A receptor disulfide bridge integrity is crucial for ligand binding to different signalling states but not for its homodimerization.

The serotonin 2 (5-HT) receptor is a G-protein coupled receptor (GPCR) with a conserved disulfide bridge formed by Cys (transmembrane helix 3, TM3) and Cys (extracellular loop 2, ECL-2). We hypothesized that disulfide bridges may determine serotonin 5-HT receptor functions such as receptor activation, functional selectivity and ligand recognition. We used the reducing agent dithiothreitol (DTT) to determine how the reduction of disulfide bridges affects radioligand binding, second messenger mobilization and receptor dimerization.