Proton-driven alternating access in a spinster lipid transporter.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 09 2022
02 09 2022
Historique:
received:
21
03
2022
accepted:
16
08
2022
entrez:
2
9
2022
pubmed:
3
9
2022
medline:
9
9
2022
Statut:
epublish
Résumé
Spinster (Spns) lipid transporters are critical for transporting sphingosine-1-phosphate (S1P) across cellular membranes. In humans, Spns2 functions as the main S1P transporter in endothelial cells, making it a potential drug target for modulating S1P signaling. Here, we employed an integrated approach in lipid membranes to identify unknown conformational states of a bacterial Spns from Hyphomonas neptunium (HnSpns) and to define its proton- and substrate-coupled conformational dynamics. Our systematic study reveals conserved residues critical for protonation steps and their regulation, and how sequential protonation of these proton switches coordinates the conformational transitions in the context of a noncanonical ligand-dependent alternating access. A conserved periplasmic salt bridge (Asp60
Identifiants
pubmed: 36055994
doi: 10.1038/s41467-022-32759-2
pii: 10.1038/s41467-022-32759-2
pmc: PMC9440201
doi:
Substances chimiques
Anion Transport Proteins
0
Ligands
0
Lysophospholipids
0
Protons
0
Sphingosine
NGZ37HRE42
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5161Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM104601
Pays : United States
Organisme : NIGMS NIH HHS
ID : R24 GM145965
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
J Lipid Res. 2019 Mar;60(3):484-489
pubmed: 30655317
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W368-71
pubmed: 15980491
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
pubmed: 8744570
J Biol Chem. 2019 Aug 23;294(34):12807-12814
pubmed: 31289123
Bioinformatics. 2006 Mar 1;22(5):623-5
pubmed: 16397007
J Mol Biol. 2011 Apr 15;407(5):698-715
pubmed: 21315728
Biochim Biophys Acta. 2014 May;1841(5):759-65
pubmed: 23921254
Mol Immunol. 2018 Nov;103:55-62
pubmed: 30196234
J Phys Chem B. 2010 Jun 17;114(23):7830-43
pubmed: 20496934
Nat Commun. 2015 Sep 29;6:8393
pubmed: 26417850
J Mol Biol. 2020 Sep 18;432(20):5665-5680
pubmed: 32860775
Elife. 2020 Sep 01;9:
pubmed: 32869741
Phys Chem Chem Phys. 2011 Feb 14;13(6):2356-66
pubmed: 21116569
J Mol Biol. 2021 Aug 6;433(16):167005
pubmed: 33891902
Nature. 2021 Mar;591(7849):327-331
pubmed: 33597752
Biochim Biophys Acta. 2009 May;1794(5):738-47
pubmed: 19103310
Nat Commun. 2014 Aug 04;5:4521
pubmed: 25088546
Science. 2003 Aug 1;301(5633):616-20
pubmed: 12893936
Nat Rev Drug Discov. 2013 Sep;12(9):688-702
pubmed: 23954895
J Chem Theory Comput. 2014 Jul 8;10(7):2866-2880
pubmed: 25018675
J Gen Physiol. 2021 Nov 1;153(11):
pubmed: 34529007
Cell Res. 2015 Sep;25(9):1060-73
pubmed: 26238402
PLoS Biol. 2019 May 13;17(5):e3000260
pubmed: 31083648
J Comput Chem. 2005 Dec;26(16):1781-802
pubmed: 16222654
Protein Sci. 2015 Oct;24(10):1560-79
pubmed: 26234418
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):5870-4
pubmed: 23530251
Nature. 2017 Mar 30;543(7647):738-741
pubmed: 28289287
J Chem Phys. 2020 Jul 28;153(4):044130
pubmed: 32752662
Nat Rev Mol Cell Biol. 2003 May;4(5):397-407
pubmed: 12728273
Chem Rev. 2021 May 12;121(9):5289-5335
pubmed: 33886296
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
J Chem Inf Model. 2022 Feb 28;62(4):986-996
pubmed: 35104125
Annu Rev Phys Chem. 2012;63:419-46
pubmed: 22404592
Nat Commun. 2018 Oct 8;9(1):4151
pubmed: 30297844
FASEB J. 2015 Dec;29(12):5018-28
pubmed: 26324848
Exp Cell Res. 2015 May 1;333(2):195-200
pubmed: 25770011
Cell Rep. 2012 Nov 29;2(5):1104-10
pubmed: 23103166
Elife. 2014 May 16;3:e02740
pubmed: 24837547
Annu Rev Microbiol. 2008;62:289-305
pubmed: 18537473
Biophys J. 2009 Jul 8;97(1):50-8
pubmed: 19580743
Proc Natl Acad Sci U S A. 2020 Mar 3;117(9):4732-4740
pubmed: 32075917
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18916-21
pubmed: 24191018
J Phys Chem B. 2013 May 2;117(17):4740-54
pubmed: 23510103
Nat Struct Mol Biol. 2020 Sep;27(9):829-835
pubmed: 32719456
J Immunol. 2012 Jul 1;189(1):102-11
pubmed: 22664872
Nature. 2017 Jan 12;541(7636):233-236
pubmed: 28052056
J Cancer. 2020 May 18;11(15):4581-4588
pubmed: 32489475
J Am Chem Soc. 2021 Nov 3;143(43):17875-17890
pubmed: 34664948
Sci Rep. 2019 Dec 20;9(1):19479
pubmed: 31862903
Chem Soc Rev. 2016 Sep 21;45(18):4859-72
pubmed: 27347568
Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14664-9
pubmed: 23950222
FASEB J. 2013 Mar;27(3):1001-11
pubmed: 23180825
Nature. 1966 Aug 27;211(5052):969-70
pubmed: 5968307
Mol Membr Biol. 2004 Jul-Aug;21(4):227-36
pubmed: 15371012
Biophys J. 2010 Mar 17;98(6):L18-20
pubmed: 20303847
Cell Signal. 2021 Jan;77:109821
pubmed: 33144184
Proc Natl Acad Sci U S A. 2016 Feb 2;113(5):1220-5
pubmed: 26787875
Phys Rev Lett. 2008 Jan 18;100(2):020603
pubmed: 18232845
J Biol Chem. 2009 Mar 13;284(11):6966-71
pubmed: 19129186
J Biol Chem. 2011 Jan 21;286(3):1758-66
pubmed: 21084291
Curr Microbiol. 2015 Jun;70(6):801-9
pubmed: 25697715
Methods Enzymol. 2015;564:349-87
pubmed: 26477257
Nat Methods. 2017 Jan;14(1):71-73
pubmed: 27819658
J Chem Theory Comput. 2011 Feb 8;7(2):525-37
pubmed: 26596171
Science. 2019 May 17;364(6441):689-692
pubmed: 31097669
Annu Rev Immunol. 2012;30:69-94
pubmed: 22149932