Cryo-EM structures of human organic anion transporting polypeptide OATP1B1.
Journal
Cell research
ISSN: 1748-7838
Titre abrégé: Cell Res
Pays: England
ID NLM: 9425763
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
29
01
2023
accepted:
17
08
2023
pubmed:
7
9
2023
medline:
7
9
2023
entrez:
6
9
2023
Statut:
ppublish
Résumé
Members of the solute carrier organic anion transporting polypeptide (OATPs) family function as transporters for a large variety of amphipathic organic anions including endogenous metabolites and clinical drugs, such as bile salts, steroids, thyroid hormones, statins, antibiotics, antivirals, and anticancer drugs. OATP1B1 plays a vital role in transporting such substances into the liver for hepatic clearance. FDA and EMA recommend conducting in vitro testing of drug-drug interactions (DDIs) involving OATP1B1. However, the structure and working mechanism of OATPs still remains elusive. In this study, we determined cryo-EM structures of human OATP1B1 bound with representative endogenous metabolites (bilirubin and estrone-3-sulfate), a clinical drug (simeprevir), and a fluorescent indicator (2',7'-dichlorofluorescein), in both outward- and inward-open states. These structures reveal major and minor substrate binding pockets and conformational changes during transport. In combination with mutagenesis studies and molecular dynamics simulations, our work comprehensively elucidates the transport mechanism of OATP1B1 and provides the structural basis for DDI predictions involving OATP1B1, which will greatly promote our understanding of OATPs.
Identifiants
pubmed: 37674011
doi: 10.1038/s41422-023-00870-8
pii: 10.1038/s41422-023-00870-8
pmc: PMC10709409
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
940-951Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32171196
Informations de copyright
© 2023. The Author(s).
Références
Biopharm Drug Dispos. 2013 Jan;34(1):45-78
pubmed: 23115084
J Mol Biol. 2002 Apr 26;318(2):533-46
pubmed: 12051857
PLoS One. 2012;7(5):e36647
pubmed: 22574206
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Drug Metab Dispos. 2007 Aug;35(8):1308-14
pubmed: 17470528
Phys Rev A Gen Phys. 1985 Mar;31(3):1695-1697
pubmed: 9895674
Br J Pharmacol. 2012 Mar;165(5):1260-87
pubmed: 22013971
J Phys Chem B. 2010 Jun 17;114(23):7830-43
pubmed: 20496934
Clin Pharmacol Ther. 2013 Jul;94(1):23-6
pubmed: 23778707
Xenobiotica. 2014 Mar;44(3):276-82
pubmed: 23886114
Biochim Biophys Acta. 2003 Jan 10;1609(1):1-18
pubmed: 12507753
Nat Commun. 2022 Nov 7;13(1):6714
pubmed: 36344565
Front Genet. 2020 Oct 16;11:575678
pubmed: 33193687
Expert Opin Drug Metab Toxicol. 2020 Sep;16(9):809-822
pubmed: 32729746
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
Pharmaceutics. 2021 Oct 18;13(10):
pubmed: 34684013
N Engl J Med. 2008 Aug 21;359(8):789-99
pubmed: 18650507
Am J Physiol Gastrointest Liver Physiol. 2000 Jan;278(1):G156-64
pubmed: 10644574
Clin Pharmacol Ther. 2012 Jun;91(6):1053-64
pubmed: 22534868
Eur J Pharm Sci. 2022 Sep 1;176:106246
pubmed: 35752377
World J Gastroenterol. 2013 Oct 14;19(38):6398-407
pubmed: 24151358
Int J Mol Sci. 2018 Mar 14;19(3):
pubmed: 29538325
J Struct Biol. 2017 Jun;198(3):163-176
pubmed: 28193500
Pharm Res. 2021 Oct;38(10):1663-1675
pubmed: 34647232
PLoS One. 2013 May 22;8(5):e64069
pubmed: 23717534
Br J Pharmacol. 2009 Oct;158(3):693-705
pubmed: 19785645
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Mol Pharm. 2011 Aug 1;8(4):1303-13
pubmed: 21710988
AAPS J. 2022 Mar 21;24(3):45
pubmed: 35314909
Pflugers Arch. 2004 Feb;447(5):653-65
pubmed: 14579113
Chem Rev. 2021 May 12;121(9):5289-5335
pubmed: 33886296
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Am J Physiol Gastrointest Liver Physiol. 2007 Jul;293(1):G271-8
pubmed: 17412826
Nucleic Acids Res. 2022 Jan 7;50(D1):D439-D444
pubmed: 34791371
J Chem Inf Model. 2012 Dec 21;52(12):3144-54
pubmed: 23146088
J Nat Prod. 2013 Mar 22;76(3):368-73
pubmed: 23327877
Protein Sci. 2021 Jan;30(1):70-82
pubmed: 32881101
Pharmacol Rev. 2011 Mar;63(1):157-81
pubmed: 21245207
Mol Pharm. 2016 Feb 1;13(2):438-48
pubmed: 26696140
Biochim Biophys Acta Biomembr. 2020 May 1;1862(5):183210
pubmed: 32006472
Mol Pharm. 2022 Nov 7;19(11):4320-4332
pubmed: 36269563
Am J Physiol Cell Physiol. 2009 Mar;296(3):C570-82
pubmed: 19129463
J Biol Chem. 1997 Oct 17;272(42):26340-5
pubmed: 9334206
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Clin Pharmacol Ther. 2018 Nov;104(5):803-817
pubmed: 29679469
Clin Pharmacol Ther. 2006 Dec;80(6):565-81
pubmed: 17178259
J Struct Biol. 2005 Oct;152(1):36-51
pubmed: 16182563
Nat Struct Mol Biol. 2023 Nov;30(11):1786-1793
pubmed: 37482561
Pharm Res. 2001 Sep;18(9):1262-9
pubmed: 11683238
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Clin Pharmacokinet. 2016 Feb;55(2):197-208
pubmed: 26353895
Nat Rev Mol Cell Biol. 2016 Feb;17(2):123-32
pubmed: 26758938
Nucleic Acids Res. 2018 Jul 2;46(W1):W296-W303
pubmed: 29788355
Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60
pubmed: 10873595
Mol Pharm. 2023 Mar 6;20(3):1500-1508
pubmed: 36779498
Mol Pharm. 2017 Feb 6;14(2):359-367
pubmed: 27936768
J Biol Chem. 1998 Jun 26;273(26):16184-91
pubmed: 9632674
Annu Rev Biophys. 2015;44:257-83
pubmed: 26098515
J Biol Chem. 1999 Jun 11;274(24):17159-63
pubmed: 10358072
J Membr Biol. 2010 Aug;236(3):279-90
pubmed: 20821001
Nat Struct Mol Biol. 2023 Jul;30(7):1001-1011
pubmed: 37291422
Nat Methods. 2017 Jan;14(1):71-73
pubmed: 27819658
J Med Chem. 2012 May 24;55(10):4740-63
pubmed: 22541068
J Chem Inf Model. 2012 Dec 21;52(12):3155-68
pubmed: 23145473
Sci Adv. 2022 Nov 11;8(45):eadd7176
pubmed: 36351028
J Pharmacol Exp Ther. 2004 Oct;311(1):139-46
pubmed: 15159445
Nature. 2021 Jul;595(7869):746-750
pubmed: 34225353
Antimicrob Agents Chemother. 2014 Aug;58(8):4555-64
pubmed: 24867984
Mol Aspects Med. 2013 Apr-Jun;34(2-3):396-412
pubmed: 23506880
J Clin Invest. 2012 Feb;122(2):519-28
pubmed: 22232210