Ligand-Binding Sites in Vanilloid-Subtype TRP Channels.
TRP channels
X-ray crystallography
agonist
antagonist
blocker
cryo-EM
inhibitor
ligand
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2022
2022
Historique:
received:
21
03
2022
accepted:
06
04
2022
entrez:
2
6
2022
pubmed:
3
6
2022
medline:
3
6
2022
Statut:
epublish
Résumé
Vanilloid-subfamily TRP channels TRPV1-6 play important roles in various physiological processes and are implicated in numerous human diseases. Advances in structural biology, particularly the "resolution revolution" in cryo-EM, have led to breakthroughs in molecular characterization of TRPV channels. Structures with continuously improving resolution uncover atomic details of TRPV channel interactions with small molecules and protein-binding partners. Here, we provide a classification of structurally characterized binding sites in TRPV channels and discuss the progress that has been made by structural biology combined with mutagenesis, functional recordings, and molecular dynamics simulations toward understanding of the molecular mechanisms of ligand action. Given the similarity in structural architecture of TRP channels, 16 unique sites identified in TRPV channels may be shared between TRP channel subfamilies, although the chemical identity of a particular ligand will likely depend on the local amino-acid composition. The characterized binding sites and molecular mechanisms of ligand action create a diversity of druggable targets to aid in the design of new molecules for tuning TRP channel function in disease conditions.
Identifiants
pubmed: 35652046
doi: 10.3389/fphar.2022.900623
pii: 900623
pmc: PMC9149226
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
900623Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR078814
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA206573
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS083660
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS107253
Pays : United States
Informations de copyright
Copyright © 2022 Yelshanskaya and Sobolevsky.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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