Combined effect of confinement and affinity of crowded environment on conformation switching of adenylate kinase

AbstractThe actual conformation switching of proteins in the crowded cellular environment is completely different from that in vitro. Proteins in cytoplasm are continually subject to confinement and/or attraction to other molecules in their surroundings due to the existence of various biological species. To gain insight into the nature of crowded environments, we investigated the effects of confinement and affinity on the conformation switching of adenylate kinase (ADK) in a spherical cavity. It was found that even a small degree of confinement reduces the entropy of the open state and stabilizes the closed state, which leads to increased energy barriers for transition. Furthermore, the analysis of transition temperatures and mean first passage times indicates that the proper affinity can promote the transition of ADK from closed state to open state. This study reveals that the crowded cellular environment plays an important role in the thermodynamics and kinetics of proteins in vivo. Graphical AbstractCartoon representation of adenylate kinase in a spherical cavity. The LID, NMPand Core domains are highlighted in yellow, blue and magenta, respectively

[1]  M. Feig,et al.  Conformational sampling of peptides in the presence of protein crowders from AA/CG-multiscale simulations. , 2012, The journal of physical chemistry. B.

[2]  Marek Cieplak,et al.  Effects of confinement and crowding on folding of model proteins , 2008, Biosyst..

[3]  Allen P. Minton,et al.  Cell biology: Join the crowd , 2003, Nature.

[4]  N. Go,et al.  Studies on protein folding, unfolding, and fluctuations by computer simulation. II. A. Three‐dimensional lattice model of lysozyme , 1978 .

[5]  I. Dukovski,et al.  Langevin dynamics simulations of early stage shish-kebab crystallization of polymers in extensional flow , 2003 .

[6]  Jörg Martin.  Chaperonin function—effects of crowding and confinement , 2004, Journal of molecular recognition : JMR.

[7]  Jun Wang,et al.  Folding behavior of chaperonin‐mediated substrate protein , 2005, Proteins.

[8]  K A Dill,et al.  Stabilization of proteins in confined spaces. , 2001, Biochemistry.

[9]  Peter G Wolynes,et al.  Protein topology determines binding mechanism. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Kundu,et al.  Myoglobin unfolding in crowding and confinement. , 2012, The journal of physical chemistry. B.

[11]  A. Minton,et al.  Macromolecular crowding: biochemical, biophysical, and physiological consequences. , 1993, Annual review of biophysics and biomolecular structure.

[12]  M. Muthukumar,et al.  Langevin dynamics simulations of early-stage polymer nucleation and crystallization , 1998 .

[13]  L. Cruz,et al.  Effects of confinement on the structure and dynamics of an intrinsically disordered peptide: a molecular-dynamics study. , 2013, The journal of physical chemistry. B.

[14]  Alexander F. Christiansen,et al.  Effects of macromolecular crowding on burst phase kinetics of cytochrome c folding. , 2012, Biochemistry.

[15]  Peter G Bolhuis,et al.  Confinement-induced states in the folding landscape of the Trp-cage miniprotein. , 2012, The journal of physical chemistry. B.

[16]  Michael D. Daily,et al.  Many local motions cooperate to produce the adenylate kinase conformational transition. , 2010, Journal of molecular biology.

[17]  J. Onuchic,et al.  Topological and energetic factors: what determines the structural details of the transition state ensemble and "en-route" intermediates for protein folding? An investigation for small globular proteins. , 2000, Journal of molecular biology.

[18]  N Go,et al.  Collective variable description of native protein dynamics. , 1995, Annual review of physical chemistry.

[19]  Wei Wang,et al.  Confinement effects on the kinetics and thermodynamics of protein dimerization , 2009, Proceedings of the National Academy of Sciences.

[20]  Jun Liu,et al.  Entrapping enzyme in a functionalized nanoporous support. , 2002, Journal of the American Chemical Society.

[21]  A. Minton,et al.  Molecular crowding: analysis of effects of high concentrations of inert cosolutes on biochemical equilibria and rates in terms of volume exclusion. , 1998, Methods in enzymology.

[22]  Allen P. Minton,et al.  The effect of volume occupancy upon the thermodynamic activity of proteins: some biochemical consequences , 2004, Molecular and Cellular Biochemistry.

[23]  A. Minton,et al.  Influence of macromolecular crowding upon the stability and state of association of proteins: predictions and observations. , 2005, Journal of pharmaceutical sciences.

[24]  J. Onuchic,et al.  Funnels, pathways, and the energy landscape of protein folding: A synthesis , 1994, Proteins.

[25]  Elizabeth J. Denning,et al.  Zipping and unzipping of adenylate kinase: atomistic insights into the ensemble of open<-->closed transitions. , 2009, Journal of molecular biology.

[26]  J. Onuchic,et al.  Theory of protein folding: the energy landscape perspective. , 1997, Annual review of physical chemistry.

[27]  Mohona Sarkar,et al.  Macromolecular crowding and protein stability. , 2012, Journal of the American Chemical Society.

[28]  D Thirumalai,et al.  Simulations of β-hairpin folding confined to spherical pores using distributed computing , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Gregory A Voth,et al.  Coarse-grained free energy functions for studying protein conformational changes: a double-well network model. , 2007, Biophysical journal.

[30]  G. Pielak,et al.  Unexpected effects of macromolecular crowding on protein stability. , 2012, Biochemistry.

[31]  Qiang Lu,et al.  Single molecule conformational dynamics of adenylate kinase: energy landscape, structural correlations, and transition state ensembles. , 2008, Journal of the American Chemical Society.

[32]  Osamu Miyashita,et al.  Conformational transitions of adenylate kinase: switching by cracking. , 2007, Journal of molecular biology.

[33]  Juan J de Pablo,et al.  Confinement effects on the thermodynamics of protein folding: Monte Carlo simulations. , 2006, Biophysical journal.

[34]  A. Minton,et al.  The Influence of Macromolecular Crowding and Macromolecular Confinement on Biochemical Reactions in Physiological Media* , 2001, The Journal of Biological Chemistry.

[35]  Huan‐Xiang Zhou.  Protein folding and binding in confined spaces and in crowded solutions , 2004, Journal of molecular recognition : JMR.

[36]  J. Valentine,et al.  Molecular confinement influences protein structure and enhances thermal protein stability , 2001, Protein science : a publication of the Protein Society.

[37]  P. Wolynes.  Energy landscapes and solved protein–folding problems , 2004, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[38]  Charles L. Brooks,et al.  Insights from Coarse-Grained Gō Models for Protein Folding and Dynamics , 2009, International journal of molecular sciences.

[39]  S. Zimmerman,et al.  Estimation of macromolecule concentrations and excluded volume effects for the cytoplasm of Escherichia coli. , 1991, Journal of molecular biology.

[40]  Qiang Lu,et al.  Exploring the thermodynamic landscape, kinetics, and structural evolution of a protein conformational transition with a microscopic double-well model. , 2011, The journal of physical chemistry. B.

[41]  Hironori K. Nakamura,et al.  Scrutinizing the squeezed exponential kinetics observed in the folding simulation of an off-lattice Go-like protein model , 2004 .

[42]  W. Janke,et al.  Ground-state properties of a polymer chain in an attractive sphere. , 2012, The journal of physical chemistry. B.

[43]  Joan-Emma Shea,et al.  Effects of confinement and crowding on the thermodynamics and kinetics of folding of a minimalist β-barrel protein , 2003 .

[44]  Marek Cieplak,et al.  Folding and stretching in a Go‐like model of titin , 2001, Proteins.

[45]  Nicholas A. Kurniawan,et al.  Crowding alters the folding kinetics of a β-hairpin by modulating the stability of intermediates. , 2012, Journal of the American Chemical Society.

[46]  J. Valentine,et al.  Crowding and hydration effects on protein conformation: a study with sol-gel encapsulated proteins. , 2001, Journal of molecular biology.

[47]  K. Dill,et al.  From Levinthal to pathways to funnels , 1997, Nature Structural Biology.

[48]  Robert B. Best,et al.  Thermodynamics and kinetics of protein folding under confinement , 2008, Proceedings of the National Academy of Sciences.

[49]  Vijay S Pande,et al.  Protein folding under confinement: A role for solvent , 2007, Proceedings of the National Academy of Sciences.

[50]  Jaegil Kim,et al.  Influence of Go-like interactions on global shapes of energy landscapes in beta-barrel forming model proteins: inherent structure analysis and statistical temperature molecular dynamics simulation. , 2008, The journal of physical chemistry. B.