The structure of MgtE in the absence of magnesium provides new insights into channel gating.
Antiporters
/ chemistry
Bacterial Proteins
/ chemistry
Binding Sites
/ drug effects
Biological Transport
Cryoelectron Microscopy
Crystallography, X-Ray
Cytoplasm
/ metabolism
Ion Channel Gating
/ drug effects
Kinetics
Magnesium
/ metabolism
Models, Molecular
Protein Domains
/ drug effects
Protein Structure, Quaternary
Protein Structure, Secondary
Thermus thermophilus
/ metabolism
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
12
11
2020
accepted:
12
04
2021
revised:
07
05
2021
pubmed:
28
4
2021
medline:
25
8
2021
entrez:
27
4
2021
Statut:
epublish
Résumé
MgtE is a Mg2+ channel conserved in organisms ranging from prokaryotes to eukaryotes, including humans, and plays an important role in Mg2+ homeostasis. The previously determined MgtE structures in the Mg2+-bound, closed-state, and structure-based functional analyses of MgtE revealed that the binding of Mg2+ ions to the MgtE cytoplasmic domain induces channel inactivation to maintain Mg2+ homeostasis. There are no structures of the transmembrane (TM) domain for MgtE in Mg2+-free conditions, and the pore-opening mechanism has thus remained unclear. Here, we determined the cryo-electron microscopy (cryo-EM) structure of the MgtE-Fab complex in the absence of Mg2+ ions. The Mg2+-free MgtE TM domain structure and its comparison with the Mg2+-bound, closed-state structure, together with functional analyses, showed the Mg2+-dependent pore opening of MgtE on the cytoplasmic side and revealed the kink motions of the TM2 and TM5 helices at the glycine residues, which are important for channel activity. Overall, our work provides structure-based mechanistic insights into the channel gating of MgtE.
Identifiants
pubmed: 33905418
doi: 10.1371/journal.pbio.3001231
pii: PBIOLOGY-D-20-03338
pmc: PMC8104411
doi:
Substances chimiques
Antiporters
0
Bacterial Proteins
0
MgtE protein, bacteria
0
Magnesium
I38ZP9992A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3001231Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Methods Mol Biol. 2018;1700:97-109
pubmed: 29177828
Annu Rev Genet. 2013;47:625-46
pubmed: 24079267
Nature. 2007 Aug 30;448(7157):1072-5
pubmed: 17700703
J Am Soc Nephrol. 2013 May;24(6):967-77
pubmed: 23661805
J Am Soc Nephrol. 2008 Aug;19(8):1451-8
pubmed: 18562569
J Bacteriol. 1995 Sep;177(18):5350-4
pubmed: 7665526
Physiology (Bethesda). 2008 Oct;23:275-85
pubmed: 18927203
Science. 2017 Mar 24;355(6331):
pubmed: 28232581
Structure. 2019 Jan 2;27(1):152-160.e3
pubmed: 30318467
J Bacteriol. 1995 Mar;177(5):1233-8
pubmed: 7868596
Nat Methods. 2017 Apr;14(4):331-332
pubmed: 28250466
Nature. 2005 Jul 21;436(7049):424-7
pubmed: 16034422
Mol Aspects Med. 2013 Apr-Jun;34(2-3):620-8
pubmed: 23506895
Nature. 1990 Dec 6;348(6301):510-4
pubmed: 2174129
Nature. 1975 Aug 7;256(5517):495-7
pubmed: 1172191
Nature. 2019 May;569(7754):141-145
pubmed: 31019304
J Mol Graph. 1996 Dec;14(6):354-60, 376
pubmed: 9195488
Biometals. 2002 Sep;15(3):225-35
pubmed: 12206389
J Comput Chem. 2005 Oct;26(13):1318-28
pubmed: 16013057
J Struct Biol. 2015 Nov;192(2):216-21
pubmed: 26278980
EMBO J. 2009 Nov 18;28(22):3602-12
pubmed: 19798051
Sci Adv. 2020 Nov 18;6(47):
pubmed: 33208376
Proc Natl Acad Sci U S A. 1984 May;81(9):2772-5
pubmed: 6326143
Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15393-8
pubmed: 18832160
Cell. 2016 Feb 11;164(4):747-56
pubmed: 26871634
Nature. 2018 Aug;560(7719):447-452
pubmed: 30111839
PLoS One. 2013 Aug 15;8(8):e71096
pubmed: 23976986
Am J Physiol Cell Physiol. 2012 Jan 1;302(1):C318-26
pubmed: 22031603
Sci Rep. 2016 Jun 28;6:28565
pubmed: 27349617
Cell. 2007 Sep 7;130(5):878-92
pubmed: 17803910
Curr Top Membr. 2014;73:383-410
pubmed: 24745990
Nature. 2004 Feb 26;427(6977):803-7
pubmed: 14985752
Nat Commun. 2014 Nov 04;5:5374
pubmed: 25367295
Mutat Res. 2001 Apr 18;475(1-2):113-21
pubmed: 11295157
Cell. 2019 Apr 4;177(2):352-360.e13
pubmed: 30853217
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Nat Commun. 2017 Jul 27;8(1):148
pubmed: 28747715
Nature. 2017 Jan 26;541(7638):500-505
pubmed: 28002411
Protein Sci. 2018 Jan;27(1):135-145
pubmed: 28884485
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):352-67
pubmed: 22505256
Nature. 2018 Nov;563(7731):426-430
pubmed: 30405239
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W252-8
pubmed: 24782522
Elife. 2018 Nov 09;7:
pubmed: 30412051
Physiol Genomics. 2005 May 11;21(3):337-42
pubmed: 15713785
Biochem J. 2011 Oct 1;439(1):129-39
pubmed: 21696366
Nature. 2005 Jul 21;436(7049):420-3
pubmed: 16034421
Proc Natl Acad Sci U S A. 2018 May 8;115(19):4939-4944
pubmed: 29674445
Biochem J. 2007 Jan 15;401(2):505-13
pubmed: 16984228
Arch Biochem Biophys. 2011 Aug 1;512(1):1-23
pubmed: 21640700
Biometals. 2002 Sep;15(3):203-10
pubmed: 12206387
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4
pubmed: 24753421
Proc Natl Acad Sci U S A. 1987 Apr;84(8):2297-301
pubmed: 2436228
J Nutr. 2015 Mar;145(3):418-24
pubmed: 25733456