Hedvika Toncrova
Substrate-Modulated Thermal Fluctuations Affect Long-Range Allosteric Signaling in Protein Homodimers: Exemplified in CAP
Toncrova, Hedvika; McLeish, Tom C.B.
Authors
Tom C.B. McLeish
Abstract
The role of conformational dynamics in allosteric signaling of proteins is increasingly recognized as an important and subtle aspect of this ubiquitous phenomenon. Cooperative binding is commonly observed in proteins with twofold symmetry that bind two identical ligands. We construct a coarse-grained model of an allosteric coupled dimer and show how the signal can be propagated between the distant binding sites via change in slow global vibrational modes alone. We demonstrate that modulation on substrate binding of as few as 5–10 slow modes can give rise to cooperativity observed in biological systems and that the type of cooperativity is given by change of interaction between the two monomers upon ligand binding. To illustrate the application of the model, we apply it to a challenging test case: the catabolite activator protein (CAP). CAP displays negative cooperativity upon association with two identical ligands. The conformation of CAP is not affected by the binding, but its vibrational spectrum undergoes a strong modification. Intriguingly, the first binding enhances thermal fluctuations, yet the second quenches them. We show that this counterintuitive behavior is, in fact, necessary for an optimal anticooperative system, and captured within a well-defined region of the model's parameter space. From analyzing the experimental results, we conclude that fast local modes take an active part in the allostery of CAP, coupled to the more-global slow modes. By including them into the model, we elucidate the role of the modes on different timescales. We conclude that such dynamic control of allostery in homodimers may be a general phenomenon and that our model framework can be used for extended interpretation of thermodynamic parameters in other systems.
Citation
Toncrova, H., & McLeish, T. C. (2010). Substrate-Modulated Thermal Fluctuations Affect Long-Range Allosteric Signaling in Protein Homodimers: Exemplified in CAP. Biophysical Journal, 98(10), 2317-2326. https://doi.org/10.1016/j.bpj.2010.01.039
Journal Article Type | Article |
---|---|
Publication Date | May 1, 2010 |
Deposit Date | Nov 1, 2011 |
Publicly Available Date | Jan 23, 2013 |
Journal | Biophysical Journal |
Print ISSN | 0006-3495 |
Electronic ISSN | 1542-0086 |
Publisher | Biophysical Society |
Peer Reviewed | Peer Reviewed |
Volume | 98 |
Issue | 10 |
Pages | 2317-2326 |
DOI | https://doi.org/10.1016/j.bpj.2010.01.039 |
Files
Accepted Journal Article
(4.2 Mb)
PDF
Copyright Statement
NOTICE: this is the author’s version of a work that was accepted for publication in Biophysical journal. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biophysical journal, 98/10, 2010, 10.1016/j.bpj.2010.01.039
You might also like
Trepidation or Precession: The Turning Point in a Tradition
(2023)
Book Chapter
Commentary on the model of the world machine
(2023)
Book Chapter
The ‘allosteron’ model for entropic allostery of self-assembly
(2018)
Journal Article
Unity and Symmetry in the De Luce of Robert Grosseteste
(2016)
Book Chapter
Elasticity dominated surface segregation of small molecules in polymer mixtures
(2016)
Journal Article
Downloadable Citations
About Durham Research Online (DRO)
Administrator e-mail: dro.admin@durham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search