The molecular mechanism of phytosphingosine binding to FFAR4/GPR120 differs from that of other fatty acids.
FFAR4
GPCR
GPR120
phytosphingosine
sphingolipid
sphingosine
Journal
FEBS open bio
ISSN: 2211-5463
Titre abrégé: FEBS Open Bio
Pays: England
ID NLM: 101580716
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
14
09
2021
received:
28
07
2021
accepted:
16
09
2021
pubmed:
19
9
2021
medline:
26
3
2022
entrez:
18
9
2021
Statut:
ppublish
Résumé
Free fatty acid receptor 4 (FFAR4)/GPR120 comprises a receptor for medium- and long-chain fatty acids. We previously identified phytosphingosine (PHS) as a novel ligand of FFAR4. Although many natural FFAR4 ligands have carboxyl groups, PHS does not, thus suggesting that binding to FFAR4 is driven by a completely different mechanism than other natural ligands such as α-linolenic acid (ALA). To test this hypothesis, we performed docking simulation analysis using a FFAR4 homology model based on a protein model derived from the crystal structure of activated turkey beta-1 adrenoceptor. The docking simulation revealed that the probable hydrogen bonds to FFAR4 differ between various ligands. In particular, binding was predicted between R264 of the FFAR4 and the oxygen of the carboxylate group in ALA, as well as between E249 of the FFAR4 and the oxygen of the hydroxy group at the C4-position in PHS. Alanine substitution at E249 (E249A) dramatically reduced PHS-induced FFAR4 activation but demonstrated a weaker effect on ALA-induced FFAR4 activation. Kinetic analysis and K
Identifiants
pubmed: 34535977
doi: 10.1002/2211-5463.13301
pmc: PMC8564095
doi:
Substances chimiques
FFAR4 protein, human
0
Fatty Acids
0
Ligands
0
Receptors, G-Protein-Coupled
0
phytosphingosine
GIN46U9Q2Q
Sphingosine
NGZ37HRE42
Banques de données
RefSeq
['BC101175']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3081-3089Informations de copyright
© 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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