Vitamin E functions by association with a novel binding site on the 67 kDa laminin receptor activating diacylglycerol kinase.
67 kDa laminin receptor
diabetic nephrophaty
diacylglycerol kinase
epigallocatechin gallate
vitamin E
Journal
The Journal of nutritional biochemistry
ISSN: 1873-4847
Titre abrégé: J Nutr Biochem
Pays: United States
ID NLM: 9010081
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
27
08
2021
revised:
27
03
2022
accepted:
16
07
2022
pubmed:
18
8
2022
medline:
2
11
2022
entrez:
17
8
2022
Statut:
ppublish
Résumé
It is generally recognized that the main function of α-tocopherol (αToc), which is the most active form of vitamin E, is its antioxidant effect, while non-antioxidant effects have also been reported. We previously found that αToc ameliorates diabetic nephropathy via diacylglycerol kinase alpha (DGKα) activation in vivo, and the activation was not related to the antioxidant effect. However, the underlying mechanism of how αToc activates DGKα have been enigmatic. We report that the membrane-bound 67 kDa laminin receptor (67LR), which has previously been shown to serve as a receptor for epigallocatechin gallate (EGCG), also contains a novel binding site for vitamin E, and its association with Vitamin E mediates DGKα activation by αToc. We employed hydrogen-deuterium exchange mass spectrometry (HDX/MS) and molecular dynamics (MD) simulations to identify the specific binding site of αToc on the 67LR and discovered the conformation of the specific hydrophobic pocket that accommodates αToc. Also, HDX/MS and MD simulations demonstrated the detailed binding of EGCG to a water-exposed hydrophilic site on 67LR, while in contrast αToc binds to a distinct hydrophobic site. We demonstrated that 67LR triggers an important signaling pathway mediating non-antioxidant effects of αToc, such as DGKα activation. This is the first evidence demonstrating a membrane receptor for αToc and one of the underlying mechanisms of a non-antioxidant function for αToc.
Identifiants
pubmed: 35977663
pii: S0955-2863(22)00197-8
doi: 10.1016/j.jnutbio.2022.109129
pmc: PMC10243646
mid: NIHMS1892528
pii:
doi:
Substances chimiques
Diacylglycerol Kinase
EC 2.7.1.107
Vitamin E
1406-18-4
Receptors, Laminin
0
Catechin
8R1V1STN48
alpha-Tocopherol
H4N855PNZ1
Antioxidants
0
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
109129Subventions
Organisme : NIGMS NIH HHS
ID : F32 GM020501
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM020501
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM139641
Pays : United States
Informations de copyright
Copyright © 2022. Published by Elsevier Inc.
Références
Free Radic Biol Med. 2000 Nov 1;29(9):834-45
pubmed: 11063909
Mol Aspects Med. 2007 Oct-Dec;28(5-6):423-36
pubmed: 17320165
J Cell Biochem. 1998 Jun 1;69(3):244-51
pubmed: 9581863
Biosci Biotechnol Biochem. 2018 Jan;82(1):65-73
pubmed: 29297254
J Biol Chem. 2008 Nov 7;283(45):31227-36
pubmed: 18753135
JAMA. 2003 Jul 23;290(4):476-85
pubmed: 12876090
Biol Rev Camb Philos Soc. 2016 May;91(2):288-310
pubmed: 25630983
Free Radic Biol Med. 2007 Jul 1;43(1):4-15
pubmed: 17561088
J Med Chem. 2004 Mar 25;47(7):1750-9
pubmed: 15027866
Arch Biochem Biophys. 2008 Aug 15;476(2):133-8
pubmed: 18358230
Biochemistry. 2004 Apr 13;43(14):4143-9
pubmed: 15065857
J Biol Chem. 1999 Apr 23;274(17):11447-50
pubmed: 10206945
Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14713-8
pubmed: 14657365
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
pubmed: 8744570
J Comput Aided Mol Des. 2013 Mar;27(3):221-34
pubmed: 23579614
J Biol Chem. 1991 Apr 5;266(10):6188-94
pubmed: 2007576
BMC Complement Altern Med. 2014 Dec 06;14:469
pubmed: 25480449
J Comput Chem. 2010 Mar;31(4):671-90
pubmed: 19575467
J Lipid Res. 1993 Mar;34(3):343-58
pubmed: 8468520
J Cell Biol. 1983 May;96(5):1475-9
pubmed: 6302102
Cancer Lett. 2013 Jun 28;334(1):79-85
pubmed: 23403075
FEBS Lett. 1997 Jun 2;409(1):105-8
pubmed: 9199513
J Pathol. 1996 Aug;179(4):376-80
pubmed: 8869283
J Natl Cancer Inst. 1991 Jan 2;83(1):29-36
pubmed: 1824600
Biochem Pharmacol. 2003 Jan 15;65(2):269-73
pubmed: 12504802
J Chem Theory Comput. 2016 Jan 12;12(1):405-13
pubmed: 26631602
Nat Struct Mol Biol. 2004 Apr;11(4):380-1
pubmed: 15024383
Biochem Biophys Res Commun. 2005 Oct 21;336(2):674-81
pubmed: 16140266
BMC Cancer. 2006 Jan 17;6:13
pubmed: 16417629
J Surg Res. 2000 Sep;93(1):163-70
pubmed: 10945959
J Biol Chem. 2008 Feb 8;283(6):3050-3058
pubmed: 18079119
J Am Chem Soc. 2018 Mar 7;140(9):3285-3291
pubmed: 29342349
J Comput Chem. 2005 Dec;26(16):1781-802
pubmed: 16222654
J Am Soc Nephrol. 1997 Mar;8(3):426-35
pubmed: 9071711
Cancer Res. 1985 Jun;45(6):2713-9
pubmed: 3157447
Biochem Biophys Res Commun. 1983 Mar 29;111(3):804-8
pubmed: 6301485
FEBS Lett. 1991 Aug 19;288(1-2):41-5
pubmed: 1879562
Bioorg Med Chem. 2016 Oct 15;24(20):4801-4811
pubmed: 27320659
Cell. 1992 Feb 7;68(3):533-44
pubmed: 1531449
Clin Cancer Res. 2002 Mar;8(3):863-9
pubmed: 11895920
JAMA. 2009 Jan 7;301(1):39-51
pubmed: 19066370
J Med Chem. 2016 May 12;59(9):4403-14
pubmed: 27087127
Ann N Y Acad Sci. 2004 Dec;1031:44-59
pubmed: 15753133
Sci Rep. 2017 Jun 1;7(1):2597
pubmed: 28572624
J Lipid Res. 2015 Aug;56(8):1543-50
pubmed: 26026069
EMBO J. 1983;2(6):861-5
pubmed: 16453457
Cancer Epidemiol Biomarkers Prev. 1995 Jun;4(4):393-9
pubmed: 7655336
PLoS One. 2012;7(5):e37942
pubmed: 22666419
EMBO J. 2001 Nov 1;20(21):5863-75
pubmed: 11689427
Nat Methods. 2019 Jul;16(7):595-602
pubmed: 31249422
J Biol Chem. 2009 Jun 5;284(23):15826-34
pubmed: 19351882
J Clin Invest. 2013 Feb;123(2):787-99
pubmed: 23348740
Nat Genet. 1995 Feb;9(2):141-5
pubmed: 7719340
Sci Rep. 2020 Jul 16;10(1):11790
pubmed: 32678222
Biosci Rep. 2008 Feb;28(1):33-48
pubmed: 18269348
Genes Cells. 2005 Apr;10(4):311-9
pubmed: 15773894
J Phys Chem B. 2010 Jun 17;114(23):7830-43
pubmed: 20496934
J Biol Chem. 2008 Feb 8;283(6):3002-3005
pubmed: 18063583
J Virol. 1992 Aug;66(8):4992-5001
pubmed: 1385835
Curr Protoc Protein Sci. 2002 Aug;Chapter 17:17.6.1-17.6.18
pubmed: 18429224
J Biol Chem. 1991 Oct 25;266(30):20440-6
pubmed: 1834645
Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12190-4
pubmed: 8618868
J Biol Chem. 2014 Nov 21;289(47):32671-81
pubmed: 25294877
Prog Lipid Res. 2000 May;39(3):231-55
pubmed: 10799717
J Comput Chem. 2014 Oct 15;35(27):1997-2004
pubmed: 25130509