Structural and Dynamical Order of a Disordered Protein: Molecular Insights into Conformational Switching of PAGE4 at the Systems Level

Biomolecules
Xingcheng LinMohit Kumar Jolly

Abstract

Folded proteins show a high degree of structural order and undergo (fairly constrained) collective motions related to their functions. On the other hand, intrinsically disordered proteins (IDPs), while lacking a well-defined three-dimensional structure, do exhibit some structural and dynamical ordering, but are less constrained in their motions than folded proteins. The larger structural plasticity of IDPs emphasizes the importance of entropically driven motions. Many IDPs undergo function-related disorder-to-order transitions driven by their interaction with specific binding partners. As experimental techniques become more sensitive and become better integrated with computational simulations, we are beginning to see how the modest structural ordering and large amplitude collective motions of IDPs endow them with an ability to mediate multiple interactions with different partners in the cell. To illustrate these points, here, we use Prostate-associated gene 4 (PAGE4), an IDP implicated in prostate cancer (PCa) as an example. We first review our previous efforts using molecular dynamics simulations based on atomistic AWSEM to study the conformational dynamics of PAGE4 and how its motions change in its different physiologically r...Continue Reading

References

Jun 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·R A GoldsteinP G Wolynes
Dec 13, 1991·Science·H FrauenfelderP G Wolynes
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·J D Bryngelson, P G Wolynes
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Dec 1, 1995·Proteins·D Frishman, P Argos
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·K K KoretkeP G Wolynes
Nov 28, 2000·Proteins·P RomeroA K Dunker
May 23, 2002·Biochemistry·A Keith DunkerZoran Obradović
Oct 9, 2002·Trends in Biochemical Sciences·Peter Tompa
Feb 28, 2003·Proceedings of the National Academy of Sciences of the United States of America·Masaki Sasai, Peter G Wolynes
Oct 21, 2003·Proceedings of the National Academy of Sciences of the United States of America·O MiyashitaP G Wolynes
Mar 2, 2005·Nature Reviews. Molecular Cell Biology·H Jane Dyson, Peter E Wright
Aug 30, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tongye ShenPeter G Wolynes
Sep 15, 2005·Biochemistry·Christopher J OldfieldA Keith Dunker
Apr 19, 2006·BMC Bioinformatics·Kang PengZoran Obradovic
Aug 4, 2006·PLoS Computational Biology·Chad HaynesLilia M Iakoucheva
Aug 29, 2006·Journal of Molecular Biology·Amrita MohanVladimir N Uversky
Jan 16, 2007·Journal of Molecular Biology·Paul C WhitfordJosé N Onuchic
Jan 25, 2007·Journal of the American Chemical Society·Yaakov LevyPeter G Wolynes
May 10, 2007·Journal of Proteome Research·Vladimir VacicA Keith Dunker
Oct 31, 2007·Proceedings of the National Academy of Sciences of the United States of America·Alexander SchugJosé N Onuchic
Nov 14, 2007·The Journal of Biological Chemistry·Paul C WhitfordJosé N Onuchic
Oct 30, 2008·Cell·Arjun Raj, Alexander van Oudenaarden
Jan 27, 2010·Biochimica Et Biophysica Acta·Bin XueVladimir N Uversky
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Emmanuel TrizacPeter G Wolynes
May 19, 2010·International Journal of Molecular Sciences·Ashwini PatilHaruki Nakamura
Jul 2, 2010·Current Opinion in Structural Biology·Philip N Bryan, John Orban
Sep 16, 2010·Nature Reviews. Urology·Nicholas C Buchan, S Larry Goldenberg
Sep 29, 2011·Molecular BioSystems·Pau Bernadó, Dmitri I Svergun
Apr 14, 2012·The Journal of Physical Chemistry. B·Jeffrey K NoelJosé N Onuchic
Jul 14, 2012·Reports on Progress in Physics·Paul C WhitfordJosé N Onuchic
Nov 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Weihua ZhengPeter G Wolynes
Dec 21, 2012·Cell Cycle·Gita MahmoudabadiPrakash Kulkarni
Feb 9, 2013·European Journal of Cell Biology·Claudia T Mierke
Mar 23, 2013·Current Opinion in Structural Biology·Philip N Bryan, John Orban
Mar 29, 2013·Journal of Biomolecular Structure & Dynamics·Xiao Fan, Lukasz Kurgan
Nov 23, 2013·Biochimica Et Biophysica Acta·Krithika RajagopalanPrakash Kulkarni
Mar 13, 2014·Annual Review of Biochemistry·Christopher J Oldfield, A Keith Dunker

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Citations

Apr 14, 2019·Biomolecules·Prakash Kulkarni, Vladimir N Uversky
Apr 20, 2021·Journal of Chemical Theory and Computation·Antonio B Oliveira JuniorVitor B P Leite

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Methods Mentioned

BETA
X-ray
nuclear magnetic resonance
NMR
protein folding
PCA
xenograft

Software Mentioned

PONDR
AWSEM
AWSEM ( AAWSEM )
CHARMM36m
IUPred
AAWSEM
smFRET

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