FFAT motif phosphorylation controls formation and lipid transfer function of inter-organelle contacts.
cholesterol
inter-organelle contact
lipid transfer protein
regulation
small linear motif
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
28
12
2019
revised:
01
09
2020
accepted:
07
09
2020
pubmed:
31
10
2020
medline:
13
4
2021
entrez:
30
10
2020
Statut:
ppublish
Résumé
Organelles are physically connected in membrane contact sites. The endoplasmic reticulum possesses three major receptors, VAP-A, VAP-B, and MOSPD2, which interact with proteins at the surface of other organelles to build contacts. VAP-A, VAP-B, and MOSPD2 contain an MSP domain, which binds a motif named FFAT (two phenylalanines in an acidic tract). In this study, we identified a non-conventional FFAT motif where a conserved acidic residue is replaced by a serine/threonine. We show that phosphorylation of this serine/threonine is critical for non-conventional FFAT motifs (named Phospho-FFAT) to be recognized by the MSP domain. Moreover, structural analyses of the MSP domain alone or in complex with conventional and Phospho-FFAT peptides revealed new mechanisms of interaction. Based on these new insights, we produced a novel prediction algorithm, which expands the repertoire of candidate proteins with a Phospho-FFAT that are able to create membrane contact sites. Using a prototypical tethering complex made by STARD3 and VAP, we showed that phosphorylation is instrumental for the formation of ER-endosome contacts, and their sterol transfer function. This study reveals that phosphorylation acts as a general switch for inter-organelle contacts.
Identifiants
pubmed: 33124732
doi: 10.15252/embj.2019104369
pmc: PMC7705450
doi:
Substances chimiques
Lipids
0
MOSPD2 protein, human
0
Membrane Proteins
0
Receptors, Chemokine
0
VAPA protein, human
0
VAPB protein, human
0
Vesicular Transport Proteins
0
Banques de données
PDB
['6TQR', '6TQS', '6TQT', '6TQU']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e104369Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M011801/1
Pays : United Kingdom
Organisme : Agence Nationale de la Recherche (ANR)
ID : ANR-19-CE44-0003
Organisme : Institut National Du Cancer (INCa)
ID : INCA_9269
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P003818/1
Pays : United Kingdom
Organisme : French Infrastructure for Integrated Structural Biology (FRISBI)
ID : ANR-10-INSB-05-01
Organisme : Ligue Contre le Cancer
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
Références
Curr Opin Cell Biol. 2006 Aug;18(4):371-8
pubmed: 16806880
Apoptosis. 2006 Sep;11(9):1489-501
pubmed: 16820967
J Biol Chem. 2014 Apr 11;289(15):10748-60
pubmed: 24569996
Proc Natl Acad Sci U S A. 2017 Nov 7;114(45):12039-12044
pubmed: 29078338
Science. 2011 Oct 21;334(6054):358-62
pubmed: 21885730
Neuron. 2000 Feb;25(2):385-97
pubmed: 10719893
Nat Commun. 2014 Jun 03;5:3996
pubmed: 24893131
Mol Biol Cell. 2013 Apr;24(7):1030-40
pubmed: 23389631
Protein Sci. 2018 Jan;27(1):293-315
pubmed: 29067766
J Synchrotron Radiat. 2010 Sep;17(5):700-7
pubmed: 20724792
Mol Biol Cell. 2012 May;23(9):1765-82
pubmed: 22419818
Acta Crystallogr F Struct Biol Commun. 2014 Oct;70(Pt 10):1303-11
pubmed: 25286930
Bioinformatics. 2007 Nov 1;23(21):2947-8
pubmed: 17846036
J Cell Sci. 2013 Dec 1;126(Pt 23):5500-12
pubmed: 24105263
Biochim Biophys Acta. 2016 Aug;1861(8 Pt B):952-961
pubmed: 26898182
Hum Mol Genet. 2013 Jun 15;22(12):2350-60
pubmed: 23446633
J Biol Chem. 2006 Oct 6;281(40):30279-88
pubmed: 16895911
J Biol Chem. 2002 Dec 27;277(52):50780-7
pubmed: 12393907
J Biol Chem. 2007 Jun 15;282(24):17758-66
pubmed: 17442665
Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20
pubmed: 25514926
J Cell Biol. 2009 Jun 29;185(7):1209-25
pubmed: 19564404
BMC Bioinformatics. 2015 May 22;16:169
pubmed: 25994840
EMBO J. 2020 Dec 1;39(23):e104369
pubmed: 33124732
mBio. 2017 Jul 11;8(4):
pubmed: 28698274
Curr Opin Struct Biol. 2015 Oct;34:60-8
pubmed: 26209821
J Cell Sci. 2005 Jul 1;118(Pt 13):2791-801
pubmed: 15976441
Hum Mol Genet. 2012 Mar 15;21(6):1299-311
pubmed: 22131369
Nucleic Acids Res. 2014 Jan;42(Database issue):D358-63
pubmed: 24234451
Methods Mol Biol. 2019;1949:137-152
pubmed: 30790254
Mol Cell. 2016 Jan 7;61(1):111-24
pubmed: 26711011
J Biol Chem. 2018 Jul 13;293(28):11206-11217
pubmed: 29848549
J Neurosci. 2018 Aug 29;38(35):7562-7584
pubmed: 30012696
Biochemistry. 1981 Jul 7;20(14):4093-9
pubmed: 7284312
EMBO J. 2003 May 1;22(9):2025-35
pubmed: 12727870
Cell. 2015 Jul 16;162(2):425-440
pubmed: 26186194
Curr Opin Cell Biol. 2019 Apr;57:106-114
pubmed: 30807956
Front Mol Biosci. 2015 Oct 13;2:56
pubmed: 26528483
J Cell Biol. 2017 Feb;216(2):331-342
pubmed: 28108524
Biophys J. 2004 Jun;86(6):3993-4003
pubmed: 15189895
Annu Rev Biochem. 2015;84:791-811
pubmed: 25580528
Nat Commun. 2015 Sep 09;6:8130
pubmed: 26350500
Annu Rev Cell Dev Biol. 2019 Oct 6;35:85-109
pubmed: 31590585
Proc Natl Acad Sci U S A. 2018 Jul 31;115(31):E7331-E7340
pubmed: 29941597
J Cell Sci. 2015 Jun 1;128(11):2096-105
pubmed: 25908859
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
J Mol Recognit. 2011 Jul-Aug;24(4):511-23
pubmed: 20842623
J Cell Biol. 2020 Jun 1;219(6):
pubmed: 32346721
EMBO J. 2017 May 15;36(10):1412-1433
pubmed: 28377464
Structure. 2005 Jul;13(7):1035-45
pubmed: 16004875
Science. 2011 Aug 26;333(6046):1151-4
pubmed: 21868676
EMBO J. 2017 Nov 2;36(21):3156-3174
pubmed: 28978670
Genome Res. 2004 Jun;14(6):1188-90
pubmed: 15173120
Mol Cell. 2019 Dec 5;76(5):811-825.e14
pubmed: 31628041
J Biol Chem. 2005 Feb 18;280(7):5934-44
pubmed: 15545272
Nucleic Acids Res. 2019 Jan 8;47(D1):D529-D541
pubmed: 30476227
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):368-80
pubmed: 22505257
PLoS One. 2012;7(1):e30455
pubmed: 22276202
Dev Cell. 2014 Jul 14;30(1):86-94
pubmed: 25026035
Bioinformatics. 2009 May 1;25(9):1189-91
pubmed: 19151095
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
J Proteome Res. 2011 Dec 2;10(12):5354-62
pubmed: 22073976
J Cell Biol. 2008 May 5;181(3):497-510
pubmed: 18443221
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
EMBO Rep. 2018 Jul;19(7):
pubmed: 29858488
J Mol Biol. 1993 Jun 20;231(4):1049-67
pubmed: 8515464
J Biol Chem. 2005 May 6;280(18):17945-52
pubmed: 15718238
J Biol Chem. 2010 Apr 23;285(17):12961-70
pubmed: 20178991
Science. 2013 Oct 18;342(6156):357-60
pubmed: 24136966
Cell. 2013 Nov 7;155(4):830-43
pubmed: 24209621
Curr Biol. 2018 Apr 23;28(8):1234-1245.e4
pubmed: 29628370
Contact (Thousand Oaks). 2019 Jan;2:1-21
pubmed: 31777772
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Cell. 2016 Jul 14;166(2):408-423
pubmed: 27419871
J Mol Biol. 1968 Apr 28;33(2):491-7
pubmed: 5700707
Nature. 2017 Jun 1;546(7656):162-167
pubmed: 28538724
Nat Rev Mol Cell Biol. 2020 Jan;21(1):7-24
pubmed: 31732717
Nature. 2017 May 25;545(7655):505-509
pubmed: 28514442
Science. 2018 Aug 3;361(6401):
pubmed: 30072511
Cell Cycle. 2017 Jun 3;16(11):1039-1045
pubmed: 28463579
Biochem Biophys Rep. 2015 Sep 11;4:148-151
pubmed: 29124198
Nat Rev Mol Cell Biol. 2006 Aug;7(8):568-79
pubmed: 16936697