Thermodynamic and structural basis of phosphorylation-induced disorder-to-order transition in the regulatory light chain of smooth muscle myosin.

Journal of the American Chemical Society
L Michel Espinoza-FonsecaDavid D Thomas

Abstract

We have performed molecular dynamics simulations of the phosphorylation domain (PD) of the regulatory light chain (RLC) of smooth muscle myosin, to gain insight into the thermodynamic principles governing the phosphorylation-induced disorder-to-order transition. Simulations were performed in explicit water under near-physiological conditions, starting with an ideal alpha-helix. In the absence of phosphorylation, the helical periodicity of the peptide was disrupted at residues T9-K11, while phosphorylation significantly favored the helical periodicity, in agreement with experimental data. Using the MM/PBSA approach, we calculated a relative free energy of -7.1 kcal/mol for the disorder-to-order transition. A large enthalpic decrease was compensated by a large loss of conformational entropy, despite the small helical increase (no more than three residues) upon phosphorylation. Phosphorylation decreased the conformational dynamics of K and R side chains, especially R16, which forms a salt bridge with pS19. Mutation of R16 to A or E prevented this phosphorylation-dependent ordering. We propose that phosphorylation balances the enthalpy-entropy compensation of the disorder-to-order transition of RLC via short and long-range electros...Continue Reading

References

Feb 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·H L SweeneyK M Trybus
May 16, 2000·The Journal of Biological Chemistry·P A EllisonC R Cremo
Dec 26, 2001·Chemical Reviews·L N Johnson, R J Lewis
Jan 22, 2004·Journal of the American Chemical Society·Alexander D MacKerellCharles L Brooks
Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Wendy D NelsonDavid D Thomas
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Apr 1, 2006·Journal of Molecular Biology·Christine B KarimDavid D Thomas
Jan 25, 2007·Journal of the American Chemical Society·Daniel J MandellMatthew P Jacobson

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Citations

Apr 2, 2010·Physical Chemistry Chemical Physics : PCCP·Alvaro Cimas, Marie-Pierre Gaigeot
Apr 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·David KastDavid D Thomas
Nov 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·Brett A ColsonDavid D Thomas
May 7, 2009·Annual Review of Biophysics·David D ThomasVicci L Korman
Jan 18, 2013·PLoS Computational Biology·Stefka TyanovaDmitrij Frishman
Dec 14, 2012·PloS One·Marije Aan den ToornCarlo P M van Mierlo
Jan 19, 2010·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Vladimir VacicPredrag Radivojac
Jun 16, 2015·FEBS Letters·Rebecca B BerlowPeter E Wright
Feb 8, 2016·Current Genetics·R Nostramo, P K Herman
Mar 23, 2011·Journal of Molecular Biology·Hyun Suk JungPeter J Knight
Mar 1, 2016·Chemical Reviews·Veronika CsizmokJulie D Forman-Kay
Sep 23, 2009·Journal of Molecular Biology·Daniel M HimmelCarolyn Cohen
Apr 3, 2009·Current Opinion in Structural Biology·Arjun Narayanan, Matthew P Jacobson
Feb 13, 2010·Journal of Molecular Recognition : JMR·V ZoeteO Michielin
Aug 29, 2014·Journal of Cellular Biochemistry·Ziv Radisavljevic
Jul 31, 2013·Biochimica Et Biophysica Acta·Gaetano InvernizziElena Papaleo
Apr 17, 2016·European Biophysics Journal : EBJ·Haiyang YuMichael A Ferenczi
Dec 24, 2013·Journal of Structural Biology·Kenneth A TaylorKathleen M Trybus
Mar 5, 2014·Biochimica Et Biophysica Acta·Luzineide W TinocoCristina Arruti
Nov 10, 2011·Biophysical Journal·V S Senthil KumarCarolyn Cohen
Aug 26, 2014·Frontiers in Genetics·Hafumi NishiAnna R Panchenko
Nov 5, 2016·The Journal of Physical Chemistry. B·Rainer BombliesMartin Zacharias
Jun 4, 2015·Molecular BioSystems·L Michel Espinoza-FonsecaRaúl Padrón
Aug 17, 2010·Journal of Muscle Research and Cell Motility·Andras KengyelJames R Sellers
Aug 30, 2012·Journal of Muscle Research and Cell Motility·Brett A ColsonDavid D Thomas
Oct 11, 2019·Journal of Biomolecular NMR·Ruth Hendus-AltenburgerBirthe B Kragelund
Aug 8, 2019·The Journal of General Physiology·Shixin YangRoger Craig
Apr 13, 2019·Nature Communications·Maksym TsytlonokRichard Kriwacki
Oct 4, 2018·Scientific Reports·Jacopo SgrignaniAndrea Cavalli
Apr 8, 2020·Computational and Structural Biotechnology Journal·Eli Fernández-de GortariL Michel Espinoza-Fonseca
Sep 8, 2009·Journal of Chemical Theory and Computation·A CimasM-P Gaigeot
Apr 19, 2012·The Journal of Physical Chemistry Letters·Anton A Polyansky, Bojan Zagrovic
Nov 28, 2019·Journal of Chemical Theory and Computation·Wei KangDavid J Wales

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