A cationic motif upstream Engrailed2 homeodomain controls cell internalization through selective interaction with heparan sulfates.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 04 2023
10 04 2023
Historique:
received:
11
11
2021
accepted:
29
03
2023
medline:
11
4
2023
entrez:
9
4
2023
pubmed:
10
4
2023
Statut:
epublish
Résumé
Engrailed2 (En2) is a transcription factor that transfers from cell to cell through unconventional pathways. The poorly understood internalization mechanism of this cationic protein is proposed to require an initial interaction with cell-surface glycosaminoglycans (GAGs). To decipher the role of GAGs in En2 internalization, we have quantified the entry of its homeodomain region in model cells that differ in their content in cell-surface GAGs. The binding specificity to GAGs and the influence of this interaction on the structure and dynamics of En2 was also investigated at the amino acid level. Our results show that a high-affinity GAG-binding sequence (RKPKKKNPNKEDKRPR), upstream of the homeodomain, controls En2 internalization through selective interactions with highly-sulfated heparan sulfate GAGs. Our data underline the functional importance of the intrinsically disordered basic region upstream of En2 internalization domain, and demonstrate the critical role of GAGs as an entry gate, finely tuning homeoprotein capacity to internalize into cells.
Identifiants
pubmed: 37032404
doi: 10.1038/s41467-023-37757-6
pii: 10.1038/s41467-023-37757-6
pmc: PMC10083169
doi:
Substances chimiques
Heparitin Sulfate
9050-30-0
Glycosaminoglycans
0
Transcription Factors
0
Homeodomain Proteins
0
Sulfates
0
Chondroitin Sulfates
9007-28-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1998Informations de copyright
© 2023. The Author(s).
Références
Trends Genet. 1996 Jan;12(1):15-20
pubmed: 8741855
Cell Mol Life Sci. 2015 Feb;72(4):809-20
pubmed: 25112713
Glycobiology. 2015 Sep;25(9):976-83
pubmed: 26033936
Pharmacol Rev. 2013 Jan 08;65(1):90-104
pubmed: 23300132
Nat Protoc. 2006;1(1):200-5
pubmed: 17406233
J Comp Neurol. 2006 Feb 1;494(4):559-77
pubmed: 16374793
Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1864-8
pubmed: 1672046
J Biol Chem. 2007 Mar 23;282(12):8994-9000
pubmed: 17242404
J Biol Chem. 2009 Dec 4;284(49):33957-65
pubmed: 19833724
Am J Physiol Cell Physiol. 2022 Jun 1;322(6):C1271-C1278
pubmed: 35544698
Trends Biochem Sci. 2003 Mar;28(3):145-51
pubmed: 12633994
Curr Biol. 1998 Jul 16;8(15):856-63
pubmed: 9705930
Bioinformatics. 2015 Apr 15;31(8):1325-7
pubmed: 25505092
J Biol Chem. 1994 Jul 22;269(29):18881-90
pubmed: 8034644
Mol Biosyst. 2017 May 2;13(5):852-865
pubmed: 28317949
Biophys J. 2013 Aug 6;105(3):667-78
pubmed: 23931315
Front Integr Neurosci. 2018 Feb 02;12:3
pubmed: 29456495
J Biol Chem. 2010 Aug 13;285(33):25666-76
pubmed: 20484051
PLoS One. 2019 Jan 4;14(1):e0209573
pubmed: 30608949
Biophys J. 2015 Sep 1;109(5):988-99
pubmed: 26331256
Cell Rep. 2019 Jul 16;28(3):712-722.e3
pubmed: 31315049
Chemistry. 2009 Sep 21;15(37):9579-95
pubmed: 19621396
Arteriosclerosis. 1989 Jan-Feb;9(1):21-32
pubmed: 2463827
Nature. 2005 Nov 3;438(7064):94-8
pubmed: 16267555
Biochim Biophys Acta. 2012 Nov;1818(11):2669-78
pubmed: 22705501
J Biol Chem. 1998 Sep 25;273(39):24979-82
pubmed: 9737951
Elife. 2014 Sep 08;3:e02671
pubmed: 25201875
Prog Nucl Magn Reson Spectrosc. 2013 Aug;73:1-16
pubmed: 23962882
Curr Pharm Des. 2013;19(16):2851-62
pubmed: 23140458
Exp Neurol. 2015 Dec;274(Pt B):100-14
pubmed: 26277685
Cell Rep. 2013 Jun 27;3(6):1815-23
pubmed: 23770240
J Biomol NMR. 1995 Nov;6(3):277-93
pubmed: 8520220
J Cell Sci. 2020 Jul 8;133(13):
pubmed: 32434869
Sci Rep. 2016 Nov 14;6:36938
pubmed: 27841303
J Biol Chem. 1996 Jul 26;271(30):17804-10
pubmed: 8663266
Biochem J. 1991 Feb 1;273 ( Pt 3):553-9
pubmed: 1996955
Biochim Biophys Acta. 2011 Jan;1808(1):382-93
pubmed: 20920465
Neuron. 2009 Nov 12;64(3):355-366
pubmed: 19914184
Biopolymers. 2011 Oct;95(10):722-31
pubmed: 21538329
Sci Adv. 2020 Oct 28;6(44):
pubmed: 33115744
Chem Commun (Camb). 2017 Jan 31;53(10):1743-1746
pubmed: 28106177
J Biol Chem. 2006 Jun 30;281(26):17789-800
pubmed: 16644727
Acc Chem Res. 2017 Dec 19;50(12):2968-2975
pubmed: 29172443
J Biol Chem. 1996 Jul 26;271(30):18188-93
pubmed: 8663410
Angew Chem Int Ed Engl. 2017 Jul 3;56(28):8226-8230
pubmed: 28485523
J Biol Chem. 1994 Apr 8;269(14):10444-50
pubmed: 8144628
Angew Chem Int Ed Engl. 2005 Jul 4;44(27):4244-7
pubmed: 15929148
FEBS Lett. 2013 Jun 19;587(12):1693-702
pubmed: 23669356
J Control Release. 2012 Apr 30;159(2):181-8
pubmed: 22285548
Proc Natl Acad Sci U S A. 1985 May;82(10):3197-201
pubmed: 3858816
Methods Mol Biol. 2015;1324:29-37
pubmed: 26202260
Biochemistry. 2004 Mar 9;43(9):2438-44
pubmed: 14992581
Gynecol Oncol. 2016 Mar;140(3):527-36
pubmed: 26731725
J Biomol NMR. 1995 Sep;6(2):135-40
pubmed: 8589602
FASEB J. 2013 Feb;27(2):738-49
pubmed: 23070606
J Biomol NMR. 2001 May;20(1):71-5
pubmed: 11430757
New Biol. 1991 Nov;3(11):1121-34
pubmed: 1777485
Sci Adv. 2021 Dec 24;7(52):eabl6026
pubmed: 34936441
Annu Rev Biochem. 2014;83:129-57
pubmed: 24606135
Adv Drug Deliv Rev. 2008 Mar 1;60(4-5):580-97
pubmed: 18045730
Development. 2012 Jan;139(1):215-24
pubmed: 22147955
J Neurosci. 2012 Jul 4;32(27):9429-37
pubmed: 22764251
Development. 2015 May 15;142(10):1840-9
pubmed: 25926358
Nat Rev Neurosci. 2001 Feb;2(2):99-108
pubmed: 11253000
J Cell Sci. 1992 Aug;102 ( Pt 4):717-22
pubmed: 1358900
Biomol NMR Assign. 2011 Oct;5(2):229-31
pubmed: 21516336