Arginine 125 Is an Essential Residue for the Function of MRAP2.
GPCR
MRAP2
obesity
prokineticins
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
30 Aug 2022
30 Aug 2022
Historique:
received:
29
07
2022
revised:
25
08
2022
accepted:
27
08
2022
entrez:
9
9
2022
pubmed:
10
9
2022
medline:
14
9
2022
Statut:
epublish
Résumé
MRAP2 is a small simple transmembrane protein arranged in a double antiparallel topology on the plasma membrane. It is expressed in the paraventricular nucleus of the hypothalamus, where it interacts with various G protein-coupled receptors, such as the prokineticin receptors, and regulates energy expenditure and appetite. The aim of this work was to analyze the functional role of the specific arginine residue at position 125 of MRAP2, which affects protein conformation, dimer formation, and PKR2 binding. Results obtained with the MRAP2 mutants R125H and R125C, which are found in human patients with extreme obesity, and mouse MRAP2, in which arginine 125 is normally replaced by histidine, were compared with those obtained with human MRAP2. Understanding the mechanism by which MRAP2 regulates G protein-coupled receptors helps in elucidating the metabolic pathways involved in metabolic dysfunction and in developing new drugs as specific targets of the MRAP2-PKR2 complex.
Identifiants
pubmed: 36077245
pii: ijms23179853
doi: 10.3390/ijms23179853
pmc: PMC9456287
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
MRAP2 protein, human
0
MRAP2 protein, mouse
0
Receptors, G-Protein-Coupled
0
Arginine
94ZLA3W45F
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
Gene. 2020 Oct 5;757:144949
pubmed: 32679290
J Biol Chem. 2020 Nov 27;295(48):16370-16379
pubmed: 32943551
Eur J Pharmacol. 2011 Jun 11;660(1):171-80
pubmed: 21211533
Endocrine. 2018 Jul;61(1):94-104
pubmed: 29704154
Front Neurosci. 2021 Aug 13;15:730417
pubmed: 34483834
Biomolecules. 2022 Mar 20;12(3):
pubmed: 35327666
Mol Cell Proteomics. 2010 Oct;9(10):2149-61
pubmed: 20173216
Elife. 2016 Feb 01;5:
pubmed: 26829592
Science. 2013 Jul 19;341(6143):275-8
pubmed: 23869016
Mol Cell Endocrinol. 2009 Mar 5;300(1-2):25-31
pubmed: 19028547
Cell Biochem Funct. 2021 Mar;39(2):326-334
pubmed: 32892338
Biomedicines. 2021 Nov 09;9(11):
pubmed: 34829877
Obesity (Silver Spring). 2016 Sep;24(9):1976-82
pubmed: 27474872
Cell Mol Life Sci. 2011 Sep;68(17):2919-29
pubmed: 21161321
Neuropeptides. 2018 Oct;71:32-42
pubmed: 30253862
Mol Genet Metab. 2016 Mar;117(3):383-8
pubmed: 26795956
J Biol Chem. 2009 Jan 2;284(1):610-618
pubmed: 18981183
Nat Med. 2019 Nov;25(11):1733-1738
pubmed: 31700171
Biochim Biophys Acta Mol Cell Res. 2017 Dec;1864(12):2322-2329
pubmed: 28939058
Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6146-51
pubmed: 19329486
Life (Basel). 2022 Jan 25;12(2):
pubmed: 35207461
Nat Rev Mol Cell Biol. 2015 Jan;16(1):18-29
pubmed: 25531225