Crystal structure of the human oxytocin receptor.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
03
03
2020
accepted:
29
05
2020
entrez:
25
8
2020
pubmed:
25
8
2020
medline:
12
4
2022
Statut:
epublish
Résumé
The peptide hormone oxytocin modulates socioemotional behavior and sexual reproduction via the centrally expressed oxytocin receptor (OTR) across several species. Here, we report the crystal structure of human OTR in complex with retosiban, a nonpeptidic antagonist developed as an oral drug for the prevention of preterm labor. Our structure reveals insights into the detailed interactions between the G protein-coupled receptor (GPCR) and an OTR-selective antagonist. The observation of an extrahelical cholesterol molecule, binding in an unexpected location between helices IV and V, provides a structural rationale for its allosteric effect and critical influence on OTR function. Furthermore, our structure in combination with experimental data allows the identification of a conserved neurohypophyseal receptor-specific coordination site for Mg
Identifiants
pubmed: 32832646
doi: 10.1126/sciadv.abb5419
pii: abb5419
pmc: PMC7439316
doi:
Substances chimiques
Receptors, Oxytocin
0
Oxytocin
50-56-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabb5419Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Références
Chem Phys Lipids. 2016 Sep;199:61-73
pubmed: 27108066
FEBS Lett. 2005 Jan 17;579(2):349-56
pubmed: 15642343
Psychoneuroendocrinology. 1998 Nov;23(8):779-818
pubmed: 9924738
J Endocrinol. 1998 Feb;156(2):223-9
pubmed: 9518866
Pharmacol Rev. 2012 Jul;64(3):621-44
pubmed: 22679220
Biochemistry. 1997 Sep 9;36(36):10959-74
pubmed: 9283088
Science. 2007 Nov 23;318(5854):1258-65
pubmed: 17962520
Science. 2008 Nov 7;322(5903):900-4
pubmed: 18988842
Structure. 2008 Jun;16(6):897-905
pubmed: 18547522
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):352-67
pubmed: 22505256
Mini Rev Med Chem. 2008 Sep;8(10):996-1005
pubmed: 18782052
Am J Psychiatry. 1997 Jun;154(6):726-35
pubmed: 9167498
Trends Biochem Sci. 2014 May;39(5):233-44
pubmed: 24767681
Br Med J. 1948 Jul 17;2(4567):123-7
pubmed: 18871687
Endocrinology. 1997 Jul;138(7):2829-34
pubmed: 9202224
Reprod Biomed Online. 2010 Sep;21(3):338-43
pubmed: 20638340
Sci Rep. 2016 Feb 25;6:21508
pubmed: 26911446
Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
pubmed: 15299374
Nature. 2015 Mar 12;519(7542):247-50
pubmed: 25533960
Mol Endocrinol. 2007 Feb;21(2):512-23
pubmed: 17082326
Am J Perinatol. 1989 Apr;6(2):196-9
pubmed: 2540760
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-67
pubmed: 21460454
J Biol Chem. 1996 Dec 6;271(49):31593-601
pubmed: 8940177
Nat Protoc. 2009;4(5):706-31
pubmed: 19390528
Drugs. 2004;64(4):375-82
pubmed: 14969573
Biochim Biophys Acta. 2002 Aug 31;1564(2):384-92
pubmed: 12175921
Schizophr Res. 2011 Oct;132(1):50-3
pubmed: 21840177
Science. 1982 Mar 12;215(4538):1396-8
pubmed: 6278592
Neuropsychopharmacology. 2003 Jan;28(1):193-8
pubmed: 12496956
J Biol Chem. 1995 Oct 27;270(43):25771-7
pubmed: 7592759
Structure. 2008 Mar;16(3):351-9
pubmed: 18334210
Science. 2019 May 24;364(6442):775-778
pubmed: 31072904
Curr Chem Genomics. 2009 May 28;3:22-32
pubmed: 20161833
J Biol Chem. 1979 May 25;254(10):3899-906
pubmed: 220225
Nat Commun. 2019 Jan 3;10(1):17
pubmed: 30604743
Anal Biochem. 2005 Aug 15;343(2):344-6
pubmed: 16005425
Bioorg Med Chem Lett. 2008 Jan 1;18(1):90-4
pubmed: 18032036
Med Res Rev. 2011 Jul;31(4):576-604
pubmed: 20027670
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Nature. 2018 Jun;558(7711):559-563
pubmed: 29925945
Methods. 2011 Dec;55(4):310-7
pubmed: 22041719
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14
pubmed: 23793146
Nature. 2014 May 1;509(7498):115-8
pubmed: 24670650
Biochemistry. 1995 Oct 24;34(42):13784-93
pubmed: 7577971
Science. 2010 Jan 1;327(5961):46-50
pubmed: 20044567
Biochim Biophys Acta Biomembr. 2018 Jun;1860(6):1301-1308
pubmed: 29524392
Nat Methods. 2013 Mar;10(3):259-64
pubmed: 23396283
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Biochem J. 1989 Jan 15;257(2):611-4
pubmed: 2539090
Mol Cell Endocrinol. 2011 Feb 10;333(1):20-7
pubmed: 21130837
Bioorg Med Chem Lett. 2005 May 16;15(10):2579-82
pubmed: 15863320
Acta Obstet Gynecol Scand. 1990;69(4):301-6
pubmed: 2244461
J Autism Dev Disord. 1992 Sep;22(3):449-51
pubmed: 1400106
J Biol Chem. 1953 Dec;205(2):949-57
pubmed: 13129273