Matches in SemOpenAlex for { <https://semopenalex.org/work/W2753643752> ?p ?o ?g. }
- W2753643752 endingPage "146" @default.
- W2753643752 startingPage "138" @default.
- W2753643752 abstract "The serotonin 2A (5-HT2A) receptor is a G-protein coupled receptor (GPCR) with a conserved disulfide bridge formed by Cys148 (transmembrane helix 3, TM3) and Cys227 (extracellular loop 2, ECL-2). We hypothesized that disulfide bridges may determine serotonin 5-HT2A 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. A DTT-induced decrease in the number of binding sites (1190 ± 63.55 fmol/mg protein for control cells compared with 921.2 ± 60.84 fmol/mg protein for DTT-treated cells) as well as in the efficacy of both signalling pathways characterized was observed, although the affinity and potency were unchanged. Bioluminiscence resonance energy transfer (BRET) assays revealed the DTT treatment did not modify the homodimeric nature of serotonin 5-HT2A receptors. In molecular dynamic simulations, the ECL-2 of the receptor with a broken cysteine bond adopts a wider variety of conformations, some of which protrude deeper into the receptor orthosteric binding pocket leading to collapse of the pocket. A shrunken binding pocket would be incapable of accommodating lysergic acid diethylamide (LSD). Our findings suggest that the decrease of efficacy may be due to disruption of disulfide bridge between TM3 and ECL-2. This reveals the integrity of the ECL-2 epitope, which should be explored in the development of novel ligands acting as allosteric modulators of serotonin 5-HT2A receptors." @default.
- W2753643752 created "2017-09-15" @default.
- W2753643752 creator A5001008897 @default.
- W2753643752 creator A5018243559 @default.
- W2753643752 creator A5026103807 @default.
- W2753643752 creator A5040924207 @default.
- W2753643752 creator A5042195072 @default.
- W2753643752 creator A5058712463 @default.
- W2753643752 creator A5064817004 @default.
- W2753643752 creator A5069377650 @default.
- W2753643752 creator A5078882820 @default.
- W2753643752 date "2017-11-01" @default.
- W2753643752 modified "2023-10-18" @default.
- W2753643752 title "Serotonin 2A receptor disulfide bridge integrity is crucial for ligand binding to different signalling states but not for its homodimerization" @default.
- W2753643752 cites W1517863661 @default.
- W2753643752 cites W1562882205 @default.
- W2753643752 cites W1825353903 @default.
- W2753643752 cites W187159034 @default.
- W2753643752 cites W1908561802 @default.
- W2753643752 cites W1960000138 @default.
- W2753643752 cites W1969111000 @default.
- W2753643752 cites W1970613671 @default.
- W2753643752 cites W1972923838 @default.
- W2753643752 cites W1973001614 @default.
- W2753643752 cites W1976983333 @default.
- W2753643752 cites W1982309568 @default.
- W2753643752 cites W1986191025 @default.
- W2753643752 cites W1987920070 @default.
- W2753643752 cites W2003239544 @default.
- W2753643752 cites W2003872240 @default.
- W2753643752 cites W2004206813 @default.
- W2753643752 cites W2007051067 @default.
- W2753643752 cites W2012499074 @default.
- W2753643752 cites W202219468 @default.
- W2753643752 cites W2022645883 @default.
- W2753643752 cites W2023750079 @default.
- W2753643752 cites W2024942419 @default.
- W2753643752 cites W2027561572 @default.
- W2753643752 cites W2031707488 @default.
- W2753643752 cites W2037882691 @default.
- W2753643752 cites W2040489780 @default.
- W2753643752 cites W2042170152 @default.
- W2753643752 cites W2044083144 @default.
- W2753643752 cites W2048718061 @default.
- W2753643752 cites W2049611742 @default.
- W2753643752 cites W2051514715 @default.
- W2753643752 cites W2052235822 @default.
- W2753643752 cites W2071527250 @default.
- W2753643752 cites W2075165760 @default.
- W2753643752 cites W2077292282 @default.
- W2753643752 cites W2082611022 @default.
- W2753643752 cites W2083162388 @default.
- W2753643752 cites W2085460878 @default.
- W2753643752 cites W2091409146 @default.
- W2753643752 cites W2094589918 @default.
- W2753643752 cites W2104349140 @default.
- W2753643752 cites W2114748406 @default.
- W2753643752 cites W2117052111 @default.
- W2753643752 cites W2118500001 @default.
- W2753643752 cites W2121473111 @default.
- W2753643752 cites W2122098505 @default.
- W2753643752 cites W2122187061 @default.
- W2753643752 cites W2129499825 @default.
- W2753643752 cites W2132033525 @default.
- W2753643752 cites W2132461193 @default.
- W2753643752 cites W2135689740 @default.
- W2753643752 cites W2142065056 @default.
- W2753643752 cites W2149963584 @default.
- W2753643752 cites W2151343044 @default.
- W2753643752 cites W2157558738 @default.
- W2753643752 cites W2158207659 @default.
- W2753643752 cites W2164339448 @default.
- W2753643752 cites W2337026077 @default.
- W2753643752 cites W2406715792 @default.
- W2753643752 cites W2523761308 @default.
- W2753643752 cites W2524120033 @default.
- W2753643752 cites W2581696375 @default.
- W2753643752 doi "https://doi.org/10.1016/j.ejphar.2017.09.011" @default.
- W2753643752 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28899696" @default.
- W2753643752 hasPublicationYear "2017" @default.
- W2753643752 type Work @default.
- W2753643752 sameAs 2753643752 @default.
- W2753643752 citedByCount "10" @default.
- W2753643752 countsByYear W27536437522017 @default.
- W2753643752 countsByYear W27536437522019 @default.
- W2753643752 countsByYear W27536437522020 @default.
- W2753643752 countsByYear W27536437522021 @default.
- W2753643752 countsByYear W27536437522022 @default.
- W2753643752 crossrefType "journal-article" @default.
- W2753643752 hasAuthorship W2753643752A5001008897 @default.
- W2753643752 hasAuthorship W2753643752A5018243559 @default.
- W2753643752 hasAuthorship W2753643752A5026103807 @default.
- W2753643752 hasAuthorship W2753643752A5040924207 @default.
- W2753643752 hasAuthorship W2753643752A5042195072 @default.
- W2753643752 hasAuthorship W2753643752A5058712463 @default.
- W2753643752 hasAuthorship W2753643752A5064817004 @default.
- W2753643752 hasAuthorship W2753643752A5069377650 @default.
- W2753643752 hasAuthorship W2753643752A5078882820 @default.