Characterisation of HOIP RBR E3 ligase conformational dynamics using integrative modelling.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 09 2022
08 09 2022
Historique:
received:
21
05
2022
accepted:
22
08
2022
entrez:
8
9
2022
pubmed:
9
9
2022
medline:
14
9
2022
Statut:
epublish
Résumé
Multidomain proteins composed of individual domains connected by flexible linkers pose a challenge for structural studies due to their intrinsic conformational dynamics. Integrated modelling approaches provide a means to characterise protein flexibility by combining experimental measurements with molecular simulations. In this study, we characterise the conformational dynamics of the catalytic RBR domain of the E3 ubiquitin ligase HOIP, which regulates immune and inflammatory signalling pathways. Specifically, we combine small angle X-ray scattering experiments and molecular dynamics simulations to generate weighted conformational ensembles of the HOIP RBR domain using two different approaches based on maximum parsimony and maximum entropy principles. Both methods provide optimised ensembles that are instrumental in rationalising observed differences between SAXS-based solution studies and available crystal structures and highlight the importance of interdomain linker flexibility.
Identifiants
pubmed: 36076045
doi: 10.1038/s41598-022-18890-6
pii: 10.1038/s41598-022-18890-6
pmc: PMC9458678
doi:
Substances chimiques
Proteins
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15201Subventions
Organisme : Wellcome Trust
ID : FC001142
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001142
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T002212/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001142
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
J Am Chem Soc. 2010 Sep 29;132(38):13553-8
pubmed: 20822180
Nature. 2011 Mar 31;471(7340):591-6
pubmed: 21455173
Cell. 2019 May 30;177(6):1384-1403
pubmed: 31150619
Methods Mol Biol. 2020;2112:219-240
pubmed: 32006288
Prog Mol Biol Transl Sci. 2020;170:123-176
pubmed: 32145944
EMBO Rep. 2012 Sep;13(9):840-6
pubmed: 22791023
PLoS One. 2011;6(8):e24109
pubmed: 21909381
Structure. 2017 Jun 6;25(6):890-900.e5
pubmed: 28552575
Nat Struct Mol Biol. 2017 May;24(5):475-483
pubmed: 28414322
Nature. 2013 Nov 21;503(7476):422-426
pubmed: 24141947
Eur Biophys J. 2011 Jul;40(7):843-56
pubmed: 21533652
J Am Chem Soc. 2013 Nov 6;135(44):16595-609
pubmed: 24093873
J Chem Theory Comput. 2017 Jun 13;13(6):2418-2429
pubmed: 28482663
Chem Rev. 2016 Jun 8;116(11):6391-423
pubmed: 26889708
Nature. 2011 Mar 31;471(7340):633-6
pubmed: 21455180
J Appl Crystallogr. 2017 Jun 26;50(Pt 4):1212-1225
pubmed: 28808438
Nat Commun. 2013;4:1983
pubmed: 23770917
Biopolymers. 2011 Aug;95(8):559-71
pubmed: 21509745
Biophys J. 2019 Aug 6;117(3):399-407
pubmed: 31337549
J Chem Theory Comput. 2018 Dec 11;14(12):6632-6641
pubmed: 30428663
Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15757-62
pubmed: 20798061
Methods Enzymol. 2011;487:545-74
pubmed: 21187238
Phys Chem Chem Phys. 2016 Feb 17;18(8):5686-701
pubmed: 26565805
J Chem Theory Comput. 2012 Oct 9;8(10):3705-23
pubmed: 26593015
Biopolymers. 2005;80(6):736-46
pubmed: 15880774
J Chem Theory Comput. 2016 Dec 13;12(12):6130-6146
pubmed: 27802394
Curr Opin Struct Biol. 2017 Feb;42:106-116
pubmed: 28063280
Biochem Soc Trans. 2022 Feb 28;50(1):541-554
pubmed: 35129612
Annu Rev Biochem. 2001;70:503-33
pubmed: 11395416
Nat Methods. 2009 Aug;6(8):551-2
pubmed: 19644455
Cell Chem Biol. 2020 Jan 16;27(1):83-93.e9
pubmed: 31813847
PLoS Comput Biol. 2020 Apr 27;16(4):e1007870
pubmed: 32339173
Biochem J. 2014 Mar 15;458(3):421-37
pubmed: 24576094
J Chem Theory Comput. 2016 Jan 12;12(1):274-80
pubmed: 26675644
Structure. 2013 Jun 4;21(6):1030-41
pubmed: 23707686
EMBO J. 2013 Jul 31;32(15):2099-112
pubmed: 23727886
Nat Commun. 2013;4:1982
pubmed: 23770887
Nat Rev Mol Cell Biol. 2007 Apr;8(4):319-30
pubmed: 17356578
J Comput Chem. 2004 Oct;25(13):1656-76
pubmed: 15264259
Curr Opin Struct Biol. 2004 Apr;14(2):208-16
pubmed: 15093836
Nat Commun. 2017 Aug 8;8(1):211
pubmed: 28790309
Nature. 2011 Mar 31;471(7340):637-41
pubmed: 21455181
J Chem Theory Comput. 2019 May 14;15(5):3390-3401
pubmed: 30939006
Nat Struct Mol Biol. 2018 Jun;25(6):440-445
pubmed: 29735995
J Chem Phys. 2007 Jan 7;126(1):014101
pubmed: 17212484
EMBO Rep. 2016 Aug;17(8):1221-35
pubmed: 27312108
Nature. 2016 Jan 28;529(7587):546-50
pubmed: 26789245
Science. 2013 Jun 21;340(6139):1451-5
pubmed: 23661642
Annu Rev Biochem. 1998;67:425-79
pubmed: 9759494
Sci Rep. 2018 Jan 8;8(1):68
pubmed: 29311602