Fluorescent non-canonical amino acid provides insight into the human serotonin transporter.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 Oct 2024
27 Oct 2024
Historique:
received:
12
01
2024
accepted:
17
10
2024
medline:
28
10
2024
pubmed:
28
10
2024
entrez:
28
10
2024
Statut:
epublish
Résumé
The serotonin transporter (SERT), responsible for the reuptake of released serotonin, serves as a major target for antidepressants and psychostimulants. Nevertheless, refining the mechanistic models for SERT remains challenging. Here, we expand the molecular understanding of the binding of ions, substrates, and inhibitors to SERT by incorporating the fluorescent non-canonical amino acid Anap through genetic code expansion. We elucidate steady-state changes in conformational dynamics of purified SERT with Anap inserted at intracellular- or extracellular sites. This uncovers the competitive mechanisms underlying cation binding and assigns distinct binding- and allosteric coupling patterns for several inhibitors and substrates. Finally, we track in real-time conformational transitions in response to the interaction with Na
Identifiants
pubmed: 39463388
doi: 10.1038/s41467-024-53584-9
pii: 10.1038/s41467-024-53584-9
doi:
Substances chimiques
Serotonin Plasma Membrane Transport Proteins
0
Serotonin
333DO1RDJY
Amino Acids
0
SLC6A4 protein, human
0
Sodium
9NEZ333N27
Fluorescent Dyes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9267Subventions
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF22OC0079091
Organisme : Sundhed og Sygdom, Det Frie Forskningsråd (Medical Sciences, Danish Council for Independent Research)
ID : 1030-00036B
Organisme : Carlsbergfondet (Carlsberg Foundation)
ID : CF20-0345
Informations de copyright
© 2024. The Author(s).
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