Membrane orientation and oligomerization of the melanocortin receptor accessory protein 2.
G protein–coupled receptor (GPCR)
accessory protein
melanocortin receptor
membrane protein
membrane threading
metabolic regulation
obesity
transmembrane domain
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:
27 11 2020
27 11 2020
Historique:
received:
03
08
2020
revised:
08
09
2020
pubmed:
19
9
2020
medline:
10
3
2021
entrez:
18
9
2020
Statut:
ppublish
Résumé
The melanocortin receptor accessory protein 2 (MRAP2) plays a pivotal role in the regulation of several G protein-coupled receptors that are essential for energy balance and food intake. MRAP2 loss-of-function results in obesity in mammals. MRAP2 and its homolog MRAP1 have an unusual membrane topology and are the only known eukaryotic proteins that thread into the membrane in both orientations. In this study, we demonstrate that the conserved polybasic motif that dictates the membrane topology and dimerization of MRAP1 does not control the membrane orientation and dimerization of MRAP2. We also show that MRAP2 dimerizes through its transmembrane domain and can form higher-order oligomers that arrange MRAP2 monomers in a parallel orientation. Investigating the molecular details of MRAP2 structure is essential for understanding the mechanism by which it regulates G protein-coupled receptors and will aid in elucidating the pathways involved in metabolic dysfunction.
Identifiants
pubmed: 32943551
pii: S0021-9258(17)50456-1
doi: 10.1074/jbc.RA120.015482
pmc: PMC7705299
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
MRAP2 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
16370-16379Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK020572
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK070332
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK110403
Pays : United States
Informations de copyright
© 2020 Chen et al.
Déclaration de conflit d'intérêts
Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article.
Références
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20244-9
pubmed: 18077336
J Mol Biol. 2002 Apr 5;317(4):591-600
pubmed: 11955011
J Biol Chem. 2008 May 2;283(18):12276-83
pubmed: 18321856
J Clin Invest. 2000 Jul;106(2):271-9
pubmed: 10903343
Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13658-63
pubmed: 16954199
Proc Int Conf Intell Syst Mol Biol. 1998;6:175-82
pubmed: 9783223
Sci Signal. 2010 Apr 06;3(116):ra28
pubmed: 20371771
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
Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4342-7
pubmed: 15753308
Biochemistry. 2015 Aug 25;54(33):5125-35
pubmed: 26244771
Mol Metab. 2018 Dec;18:79-87
pubmed: 30352741
Proc Natl Acad Sci U S A. 1989 Aug;86(15):5786-90
pubmed: 2762295
Nature. 1998 May 28;393(6683):333-9
pubmed: 9620797
J Biol Chem. 2009 Jan 2;284(1):610-8
pubmed: 18981183
EMBO J. 1986 Nov;5(11):3021-7
pubmed: 16453726
Nat Struct Mol Biol. 2006 Feb;13(2):112-6
pubmed: 16429150
J Mol Biol. 2000 Feb 25;296(3):921-36
pubmed: 10677292
Nat Commun. 2017 Sep 28;8(1):713
pubmed: 28959025
J Biol Chem. 2001 Nov 9;276(45):42182-90
pubmed: 11535606
Mol Genet Metab. 2016 Mar;117(3):383-8
pubmed: 26795956
Nat Med. 2019 Nov;25(11):1733-1738
pubmed: 31700171
J Clin Invest. 2000 Jul;106(2):253-62
pubmed: 10903341
J Biol Chem. 2015 Nov 13;290(46):27972-85
pubmed: 26424796
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
Science. 2013 Jul 19;341(6143):278-81
pubmed: 23869017
Obesity (Silver Spring). 2016 Sep;24(9):1976-82
pubmed: 27474872
Sci Signal. 2020 Jan 07;13(613):
pubmed: 31911434
FEBS J. 2016 Dec;283(24):4424-4451
pubmed: 27350538
Nat Protoc. 2006;1(1):418-28
pubmed: 17406264