Implications of an Improved Model of the TSH Receptor Transmembrane Domain (TSHR-TMD-TRIO).
Monte Carlo
TSHR
antagonist
molecular dynamics
small molecule
transmembrane
Journal
Endocrinology
ISSN: 1945-7170
Titre abrégé: Endocrinology
Pays: United States
ID NLM: 0375040
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
received:
12
01
2021
pubmed:
12
3
2021
medline:
8
10
2021
entrez:
11
3
2021
Statut:
ppublish
Résumé
The thyroid-stimulating hormone receptor (TSHR) is a G-protein-coupled receptor group A family member with 7 transmembrane helices. We generated 3 new models of its entire transmembrane region using a 600 ns molecular simulation. The simulation started from our previously published model, which we have now revised by also modeling the intracellular loops and the C-terminal tail, adding internal waters and embedding it into a lipid bilayer with a water layer and with ions added to complete the system. We have named this model TSHR-TMD-TRIO since 3 representative dominant structures were then extracted from the simulation trajectory and compared with the original model. These structures each showed small but significant changes in the relative positions of the helices. The 3 models were also used as targets to dock a set of small molecules that are known active compounds including a new TSHR antagonist (BT362), which confirmed the appropriateness of the model with some small molecules showing significant preference for one or other of the structures.
Identifiants
pubmed: 33693584
pii: 6161546
doi: 10.1210/endocr/bqab051
pmc: PMC8183494
pii:
doi:
Substances chimiques
Receptors, Thyrotropin
0
Thyrotropin
9002-71-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : BLRD VA
ID : I01 BX000800
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK069713
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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