Exchange of water for sterol underlies sterol egress from a StARkin domain.
Antiporters
/ chemistry
DNA-Binding Proteins
Endoplasmic Reticulum
/ enzymology
Exosome Multienzyme Ribonuclease Complex
Homeostasis
Membrane Proteins
/ chemistry
Molecular Dynamics Simulation
Nuclear Proteins
Protein Conformation
Protein Domains
RNA-Binding Proteins
Saccharomyces cerevisiae
/ enzymology
Saccharomyces cerevisiae Proteins
/ chemistry
Sterols
/ metabolism
Water
/ metabolism
S. cerevisiae
StART domain
biochemistry
chemical biology
lipid transport
molecular dynamics
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
04 12 2019
04 12 2019
Historique:
received:
11
11
2019
accepted:
29
11
2019
pubmed:
5
12
2019
medline:
27
5
2020
entrez:
5
12
2019
Statut:
epublish
Résumé
Previously we identified Lam/GramD1 proteins, a family of endoplasmic reticulum membrane proteins with sterol-binding StARkin domains that are implicated in intracellular sterol homeostasis. Here, we show how these proteins exchange sterol molecules with membranes. An aperture at one end of the StARkin domain enables sterol to enter/exit the binding pocket. Strikingly, the wall of the pocket is longitudinally fractured, exposing bound sterol to solvent. Large-scale atomistic molecular dynamics simulations reveal that sterol egress involves widening of the fracture, penetration of water into the cavity, and consequent destabilization of the bound sterol. The simulations identify polar residues along the fracture that are important for sterol release. Their replacement with alanine affects the ability of the StARkin domain to bind sterol, catalyze inter-vesicular sterol exchange and alleviate the nystatin-sensitivity of
Identifiants
pubmed: 31799930
doi: 10.7554/eLife.53444
pii: 53444
pmc: PMC6940019
doi:
pii:
Substances chimiques
Antiporters
0
DNA-Binding Proteins
0
LRP1 protein, S cerevisiae
0
LTC1 protein, S cerevisiae
0
Membrane Proteins
0
Nuclear Proteins
0
RNA-Binding Proteins
0
Saccharomyces cerevisiae Proteins
0
Sterols
0
Water
059QF0KO0R
Exosome Multienzyme Ribonuclease Complex
EC 3.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : R37 AG019391
Pays : United States
Organisme : NIH HHS
ID : R37AG019391
Pays : United States
Informations de copyright
© 2019, Khelashvili et al.
Déclaration de conflit d'intérêts
GK, NC, KP, DE, AM No competing interests declared
Références
Curr Opin Cell Biol. 2010 Aug;22(4):422-9
pubmed: 20627678
Mol Biol Cell. 2018 Aug 15;29(17):2128-2136
pubmed: 29927351
J Chem Theory Comput. 2016 Jan 12;12(1):405-13
pubmed: 26631602
Phys Rev Lett. 1994 Jun 6;72(23):3634-3637
pubmed: 10056251
Trends Biochem Sci. 2017 Feb;42(2):90-97
pubmed: 27956059
Biochem Biophys Res Commun. 2018 Jan 15;495(3):2270-2274
pubmed: 29274338
Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E856-E865
pubmed: 29339490
Proteins. 2009 May 1;75(2):468-77
pubmed: 18937371
Eukaryot Cell. 2009 Feb;8(2):161-9
pubmed: 19060182
BMC Biol. 2018 Mar 14;16(1):31
pubmed: 29540172
Cell Rep. 2015 Jul 7;12(1):7-14
pubmed: 26119743
J Cell Biol. 2015 May 25;209(4):539-48
pubmed: 25987606
Structure. 2018 Feb 6;26(2):356-367.e3
pubmed: 29290486
Nat Commun. 2018 Aug 14;9(1):3251
pubmed: 30108217
J Cell Sci. 2005 Jul 1;118(Pt 13):2791-801
pubmed: 15976441
Methods Mol Biol. 2019;1949:115-136
pubmed: 30790253
Nature. 2005 Sep 1;437(7055):154-8
pubmed: 16136145
Biochem Soc Trans. 2016 Apr 15;44(2):517-27
pubmed: 27068964
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W382-8
pubmed: 15980494
Sci Rep. 2017 Jan 06;7:40076
pubmed: 28059145
J Comput Chem. 2005 Dec;26(16):1781-802
pubmed: 16222654
Elife. 2015 May 22;4:null
pubmed: 26001273
ACS Chem Neurosci. 2015 Nov 18;6(11):1825-37
pubmed: 26255829
Biophys J. 2009 Jul 8;97(1):50-8
pubmed: 19580743
J Biol Chem. 2018 Apr 13;293(15):5522-5531
pubmed: 29463678
J Chem Theory Comput. 2009 Jun 9;5(6):1632-9
pubmed: 26609855
Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10037-41
pubmed: 11517324
J Chem Theory Comput. 2013 Apr 9;9(4):2000-2009
pubmed: 23750122
J Chem Phys. 2011 Feb 14;134(6):065101
pubmed: 21322734
Biochemistry. 2015 Aug 4;54(30):4623-36
pubmed: 26168008
EMBO J. 2018 Mar 15;37(6):
pubmed: 29467216
Nature. 2014 Jun 5;510(7503):48-57
pubmed: 24899304
Curr Opin Cell Biol. 2018 Aug;53:37-43
pubmed: 29783105
Curr Protoc Bioinformatics. 2006 Oct;Chapter 5:Unit-5.6
pubmed: 18428767
PLoS Biol. 2018 May 21;16(5):e2003864
pubmed: 29782498
Mol Cell. 2008 Jun 20;30(6):667-77
pubmed: 18570870
J Chem Phys. 2013 Jul 7;139(1):015102
pubmed: 23822324
Methods Mol Biol. 2019;1860:15-31
pubmed: 30317496
Cell. 2018 Oct 4;175(2):514-529.e20
pubmed: 30220461
Nat Rev Mol Cell Biol. 2019 Feb;20(2):85-101
pubmed: 30337668