Cyclophilin A allows the allosteric regulation of a structural motif in the disordered domain 2 of NS5A and thereby fine-tunes HCV RNA replication.
RNA replication
allosteric regulation
conformer ensemble
cyclophilin
hepatitis C virus (HCV)
intrinsically disordered protein
nonstructural protein 5A (NS5A)
nuclear magnetic resonance (NMR)
prolyl isomerase
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
30 08 2019
30 08 2019
Historique:
received:
27
05
2019
revised:
28
06
2019
pubmed:
19
7
2019
medline:
31
3
2020
entrez:
19
7
2019
Statut:
ppublish
Résumé
Implicated in numerous human diseases, intrinsically disordered proteins (IDPs) are dynamic ensembles of interconverting conformers that often contain many proline residues. Whether and how proline conformation regulates the functional aspects of IDPs remains an open question, however. Here, we studied the disordered domain 2 of nonstructural protein 5A (NS5A-D2) of hepatitis C virus (HCV). NS5A-D2 comprises a short structural motif (PW-turn) embedded in a proline-rich sequence, whose interaction with the human prolyl isomerase cyclophilin A (CypA) is essential for viral RNA replication. Using NMR, we show here that the PW-turn motif exists in a conformational equilibrium between folded and disordered states. We found that the fraction of conformers in the NS5A-D2 ensemble that adopt the structured motif is allosterically modulated both by the
Identifiants
pubmed: 31315928
pii: S0021-9258(20)43249-1
doi: 10.1074/jbc.RA119.009537
pmc: PMC6721930
pii:
doi:
Substances chimiques
RNA, Viral
0
Viral Nonstructural Proteins
0
NS-5 protein, hepatitis C virus
EC 2.7.7.48
Cyclophilin A
EC 5.2.1.-
Banques de données
PDB
['6HT4']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13171-13185Informations de copyright
© 2019 Dujardin et al.
Références
J Biomol NMR. 1999 Mar;13(3):289-302
pubmed: 10212987
Science. 1999 Jul 2;285(5424):110-3
pubmed: 10390360
Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13034-9
pubmed: 10557268
Trends Biochem Sci. 2000 Mar;25(3):147-50
pubmed: 10694887
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5247-52
pubmed: 11929983
J Virol. 2002 Jun;76(12):5974-84
pubmed: 12021330
Trends Biochem Sci. 2002 Oct;27(10):527-33
pubmed: 12368089
J Mol Biol. 2004 May 14;338(5):1015-26
pubmed: 15111064
J Biol Chem. 2004 Sep 24;279(39):40835-43
pubmed: 15247283
Proteins. 2005 Jan 1;58(1):45-52
pubmed: 15521057
J Biochem Mol Biol. 2004 Nov 30;37(6):741-8
pubmed: 15607035
Nature. 2005 May 19;435(7040):374-9
pubmed: 15902263
J Biol Chem. 2005 Oct 28;280(43):36417-28
pubmed: 16126720
J Comput Chem. 2005 Dec;26(16):1668-88
pubmed: 16200636
Antimicrob Agents Chemother. 2006 Sep;50(9):2976-82
pubmed: 16940091
Proteins. 2006 Nov 15;65(3):712-25
pubmed: 16981200
Nucleic Acids Res. 2007 Jan;35(Database issue):D363-6
pubmed: 17142229
Nat Rev Microbiol. 2007 Jun;5(6):453-63
pubmed: 17487147
J Proteome Res. 2007 Jun;6(6):2351-66
pubmed: 17488107
Proc Natl Acad Sci U S A. 2007 May 15;104(20):8311-5
pubmed: 17494761
Hepatology. 2007 Oct;46(4):1026-33
pubmed: 17600342
Biochemistry. 2007 Oct 16;46(41):11550-8
pubmed: 17880107
J Virol. 2008 Feb;82(3):1073-83
pubmed: 18032500
Trends Biochem Sci. 2008 Jan;33(1):2-8
pubmed: 18054235
PLoS Pathog. 2008 Mar 28;4(3):e1000035
pubmed: 18369481
J Virol. 2008 Jun;82(11):5269-78
pubmed: 18385230
Annu Rev Biophys. 2008;37:215-46
pubmed: 18573080
J Biomol NMR. 2008 Sep;42(1):11-21
pubmed: 18762868
Mol Syst Biol. 2008;4:230
pubmed: 18985028
J Virol. 2009 Feb;83(4):2044-7
pubmed: 19073742
J Virol. 2009 May;83(9):4395-403
pubmed: 19244328
Biochem Biophys Res Commun. 2009 Apr 17;381(4):634-8
pubmed: 19249289
J Biol Chem. 2009 May 15;284(20):13589-601
pubmed: 19297321
J Biol Chem. 2009 Jun 19;284(25):16998-7005
pubmed: 19380579
J Virol. 2009 Jul;83(13):6554-65
pubmed: 19386705
Cancer Sci. 2009 Oct;100(10):1943-50
pubmed: 19659609
Structure. 2009 Sep 9;17(9):1169-85
pubmed: 19748338
Nucleic Acids Res. 2010 Jan;38(Database issue):D167-80
pubmed: 19920119
Antimicrob Agents Chemother. 2010 Feb;54(2):660-72
pubmed: 19933795
PLoS One. 2010 Mar 23;5(3):e9815
pubmed: 20352119
Proteins. 2010 Jun;78(8):1950-8
pubmed: 20408171
Nature. 2010 May 6;465(7294):96-100
pubmed: 20410884
Protein Pept Lett. 2010 Aug;17(8):1012-8
pubmed: 20450484
J Hepatol. 2010 Jul;53(1):50-6
pubmed: 20451281
PLoS Pathog. 2010 Sep 23;6(9):e1001118
pubmed: 20886100
PLoS One. 2010 Oct 27;5(10):e13687
pubmed: 21060866
J Am Chem Soc. 2010 Dec 29;132(51):18000-3
pubmed: 21128621
Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6133-8
pubmed: 21444788
J Biomol NMR. 2011 May;50(1):43-57
pubmed: 21448735
J Biol Chem. 2011 Jun 10;286(23):20441-54
pubmed: 21489988
Biophys J. 2012 Feb 8;102(3):630-9
pubmed: 22325287
J Virol. 2012 May;86(9):4811-22
pubmed: 22345441
J Mol Biol. 2012 Jul 20;420(4-5):310-23
pubmed: 22543239
Antimicrob Agents Chemother. 2012 Oct;56(10):5113-21
pubmed: 22802259
Acc Chem Res. 2013 Apr 16;46(4):1039-49
pubmed: 23148796
J Biol Chem. 2012 Dec 28;287(53):44249-60
pubmed: 23152499
PLoS Pathog. 2012;8(12):e1003056
pubmed: 23236278
PLoS One. 2012;7(12):e51282
pubmed: 23251481
Curr Top Microbiol Immunol. 2013;369:113-42
pubmed: 23463199
Protein Sci. 2013 Jun;22(6):693-724
pubmed: 23553817
J Virol. 2013 Oct;87(19):10612-27
pubmed: 23885072
Virology. 2013 Sep;444(1-2):343-54
pubmed: 23896639
Molecules. 2013 Sep 04;18(9):10802-28
pubmed: 24008243
Nat Rev Mol Cell Biol. 2013 Dec;14(12):819-29
pubmed: 24150612
Gastroenterology. 2014 May;146(5):1361-72.e1-9
pubmed: 24486951
Protein Sci. 2014 Jun;23(6):723-34
pubmed: 24639329
Nature. 2014 Apr 17;508(7496):331-9
pubmed: 24740064
J Virol. 2014 Oct;88(19):11022-33
pubmed: 25031347
Bioinformatics. 2015 Apr 15;31(8):1325-7
pubmed: 25505092
Antimicrob Agents Chemother. 2015 May;59(5):2496-507
pubmed: 25666154
J Biol Chem. 2015 Jul 31;290(31):19104-20
pubmed: 26085105
J Chem Theory Comput. 2015 Aug 11;11(8):3584-3595
pubmed: 26300708
Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):14617-22
pubmed: 26553990
J Chem Theory Comput. 2013 Sep 10;9(9):3878-88
pubmed: 26592383
J Mol Biol. 2016 Jan 16;428(1):79-91
pubmed: 26655856
Nat Chem Biol. 2016 Feb;12(2):117-23
pubmed: 26656091
J Biol Chem. 2016 Mar 25;291(13):6696-705
pubmed: 26851279
Nat Commun. 2016 Mar 04;7:10714
pubmed: 26940118
J Mol Model. 2016 Apr;22(4):98
pubmed: 27037822
Lancet. 2016 Sep 10;388(10049):1081-1088
pubmed: 27394647
PLoS One. 2016 Jul 21;11(7):e0159511
pubmed: 27442520
Nat Commun. 2016 Sep 22;7:12777
pubmed: 27652979
ACS Infect Dis. 2016 Nov 11;2(11):839-851
pubmed: 27676132
Intrinsically Disord Proteins. 2013 Apr 1;1(1):e24360
pubmed: 28516008
J Biol Chem. 2017 Nov 3;292(44):18024-18043
pubmed: 28912275
Nat Rev Drug Discov. 2018 Jan;17(1):35-56
pubmed: 28935918
Nature. 2018 Mar 1;555(7694):61-66
pubmed: 29466338
J Mol Biol. 2018 Aug 3;430(16):2342-2359
pubmed: 29626537
Antimicrob Agents Chemother. 2018 Jun 26;62(7):
pubmed: 29760125
Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11519-11524
pubmed: 30333189
J Comput Chem. 2018 Sep 30;39(25):2110-2117
pubmed: 30368859
J Biomol NMR. 1994 Sep;4(5):727-34
pubmed: 7919956
Nature. 1994 Nov 24;372(6504):359-62
pubmed: 7969494
Nature. 1994 Nov 24;372(6504):363-5
pubmed: 7969495
Cell. 1993 Jun 18;73(6):1067-78
pubmed: 8513493
J Virol. 1996 Jun;70(6):3536-44
pubmed: 8648687
J Virol. 1997 Nov;71(11):8416-28
pubmed: 9343198
J Magn Reson. 1998 Apr;131(2):373-8
pubmed: 9571116
Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
pubmed: 9757107