Crystal structures of LeuT reveal conformational dynamics in the outward-facing states.
Conformational change
Membrane protein
NSS
SLC6
Structural biology
X-ray structure
monoamine transporter
tructure–function
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
Historique:
received:
23
02
2021
revised:
23
03
2021
accepted:
27
03
2021
pubmed:
4
4
2021
medline:
21
8
2021
entrez:
3
4
2021
Statut:
ppublish
Résumé
The neurotransmitter:sodium symporter (NSS) homolog LeuT from Aquifex aeolicus has proven to be a valuable model for studying the transport mechanism of the NSS family. Crystal structures have captured LeuT in key conformations visited during the transport cycle, allowing for the construction of a nearly complete model of transport, with much of the conformational dynamics studied by computational simulations. Here, we report crystal structures of LeuT representing new intermediate conformations between the outward-facing open and occluded states. These structures, combined with binding and accessibility studies, reveal details of conformational dynamics that can follow substrate binding at the central substrate binding site (S1) of LeuT in outward-facing states, suggesting a potential competition for direction between the outward-open and outward-occluded states at this stage during substrate transport. Our structures further support an intimate interplay between the protonation state of Glu290 and binding of Na1 that may ultimately regulate the outward-open-to-occluded transition.
Identifiants
pubmed: 33811858
pii: S0021-9258(21)00389-6
doi: 10.1016/j.jbc.2021.100609
pmc: PMC8105300
pii:
doi:
Substances chimiques
Bacterial Proteins
0
Plasma Membrane Neurotransmitter Transport Proteins
0
Symporters
0
Sodium
9NEZ333N27
Leucine
GMW67QNF9C
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100609Subventions
Organisme : NIDA NIH HHS
ID : R01 DA041510
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM119396
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
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