The sequence-ensemble relationship in fuzzy protein complexes.
IDP
allostery
fuzzy complexes
intrinsic disorder
protein binding
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
14 09 2021
14 09 2021
Historique:
accepted:
11
06
2021
entrez:
10
9
2021
pubmed:
11
9
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
Intrinsically disordered proteins (IDPs) interact with globular proteins through a variety of mechanisms, resulting in the structurally heterogeneous ensembles known as fuzzy complexes. While there exists a reasonable comprehension on how IDP sequence determines the unbound IDP ensemble, little is known about what shapes the structural characteristics of IDPs bound to their targets. Using a statistical thermodynamic model, we show that the target-bound ensembles are determined by a simple code that combines the IDP sequence and the distribution of IDP-target interaction hotspots. These two parameters define the conformational space of target-bound IDPs and rationalize the observed structural heterogeneity of fuzzy complexes. The presented model successfully reproduces the dynamical signatures of target-bound IDPs from the NMR relaxation experiments as well as the changes of interaction affinity and the IDP helicity induced by mutations. The model explains how the target-bound IDP ensemble adapts to mutations in order to achieve an optimal balance between conformational freedom and interaction energy. Taken together, the presented sequence-ensemble relationship of fuzzy complexes explains the different manifestations of IDP disorder in folding-upon-binding processes.
Identifiants
pubmed: 34504009
pii: 2020562118
doi: 10.1073/pnas.2020562118
pmc: PMC8449401
pii:
doi:
Substances chimiques
Intrinsically Disordered Proteins
0
Ligands
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
FEBS Lett. 2015 Sep 14;589(19 Pt A):2533-42
pubmed: 26226339
Nucleic Acids Res. 2017 May 5;45(8):4972-4983
pubmed: 28334932
Proc Natl Acad Sci U S A. 2007 May 15;104(20):8311-5
pubmed: 17494761
Nat Rev Mol Cell Biol. 2005 Mar;6(3):197-208
pubmed: 15738986
Curr Opin Struct Biol. 2019 Feb;54:19-25
pubmed: 30340123
J Mol Biol. 2020 Mar 27;432(7):2289-2303
pubmed: 32112804
Nature. 2015 Mar 5;519(7541):106-9
pubmed: 25533957
Elife. 2017 Nov 01;6:
pubmed: 29091028
Biochemistry. 2005 Sep 20;44(37):12454-70
pubmed: 16156658
Int J Mol Sci. 2016 Nov 10;17(11):
pubmed: 27834926
Nat Struct Biol. 1994 Jun;1(6):399-409
pubmed: 7664054
Nat Commun. 2019 Apr 11;10(1):1676
pubmed: 30976006
Protein Sci. 1994 May;3(5):843-52
pubmed: 8061613
J Mol Biol. 2004 May 14;338(5):1015-26
pubmed: 15111064
J Biol Chem. 2020 May 8;295(19):6586-6593
pubmed: 32253236
Biophys J. 2007 Mar 1;92(5):1439-56
pubmed: 17158572
J Am Chem Soc. 2017 Sep 6;139(35):12219-12227
pubmed: 28780862
Curr Opin Struct Biol. 2013 Jun;23(3):426-35
pubmed: 23545493
Curr Opin Struct Biol. 2019 Jun;56:1-10
pubmed: 30439585
Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9614-9
pubmed: 26195786
Biochemistry. 2019 Mar 12;58(10):1354-1362
pubmed: 30775911
J Mol Biol. 2018 Aug 3;430(16):2389-2402
pubmed: 29890118
Adv Protein Chem. 2005;72:199-226
pubmed: 16581378
Biochem J. 2013 Jan 15;449(2):307-18
pubmed: 23240611
Nat Chem Biol. 2017 Mar 22;13(4):339-342
pubmed: 28328918
Cell Mol Life Sci. 2017 Sep;74(17):3175-3183
pubmed: 28597296
Eur J Biochem. 2002 Jan;269(1):2-12
pubmed: 11784292
Angew Chem Int Ed Engl. 2017 Nov 13;56(46):14494-14497
pubmed: 28914483
Science. 2017 Sep 22;357(6357):
pubmed: 28935776
Sci Rep. 2018 May 18;8(1):7872
pubmed: 29777197
J Am Chem Soc. 2009 Feb 18;131(6):2306-12
pubmed: 19170581
Curr Opin Struct Biol. 2002 Feb;12(1):54-60
pubmed: 11839490
Curr Opin Struct Biol. 2017 Feb;42:147-154
pubmed: 28259050
Front Mol Biosci. 2018 Apr 30;5:39
pubmed: 29761107
Mol Cell. 2011 Dec 23;44(6):942-53
pubmed: 22195967
Nucleic Acids Res. 2014 Jan;42(Database issue):D326-35
pubmed: 24174539
Chem Rev. 2016 Jun 8;116(11):6424-62
pubmed: 26922996
Angew Chem Int Ed Engl. 2014 Feb 3;53(6):1548-51
pubmed: 24449148
Curr Opin Struct Biol. 2009 Feb;19(1):31-8
pubmed: 19157855
Cell Commun Signal. 2016 Jan 05;14:1
pubmed: 26727894
Methods Enzymol. 2018;611:531-557
pubmed: 30471699
Biochem Soc Trans. 2016 Oct 15;44(5):1185-1200
pubmed: 27911701
Biochemistry. 2008 Feb 5;47(5):1299-308
pubmed: 18177052
Protein Sci. 2006 Sep;15(9):2051-61
pubmed: 16882994
FEBS Lett. 2017 Sep;591(17):2682-2695
pubmed: 28762260
Curr Opin Struct Biol. 2015 Jun;32:102-12
pubmed: 25863585
J Am Chem Soc. 2013 Jan 30;135(4):1288-94
pubmed: 23289531
J Biol Chem. 2002 Nov 1;277(44):42241-8
pubmed: 12196545
Genome Inform Ser Workshop Genome Inform. 2000;11:161-71
pubmed: 11700597
Bioinform Biol Insights. 2015 Sep 21;9:141-51
pubmed: 26448684
Protein Sci. 1997 Sep;6(9):1920-36
pubmed: 9300492
Nat Chem Biol. 2014 Dec;10(12):1000-2
pubmed: 25362358
Sci Rep. 2016 Feb 25;6:21994
pubmed: 26912067
Trends Biochem Sci. 2008 Jan;33(1):2-8
pubmed: 18054235
Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13392-7
pubmed: 23901099
J Mol Biol. 2006 Oct 6;362(5):1043-59
pubmed: 16935303
Chem Rev. 2014 Jul 9;114(13):6589-631
pubmed: 24773235
J Biol Chem. 2018 Jun 22;293(25):9718-9723
pubmed: 29716994
Biochemistry. 2002 Jan 22;41(3):752-9
pubmed: 11790096
Nat Commun. 2018 Aug 20;9(1):3332
pubmed: 30127362
J Am Chem Soc. 2014 Apr 9;136(14):5197-200
pubmed: 24654952
Nat Rev Mol Cell Biol. 2015 Jan;16(1):18-29
pubmed: 25531225