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Dynamic Allostery of the Catabolite Activator Protein Revealed by Interatomic Forces.
- Source :
-
PLoS computational biology [PLoS Comput Biol] 2015 Aug 05; Vol. 11 (8), pp. e1004358. Date of Electronic Publication: 2015 Aug 05 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- The Catabolite Activator Protein (CAP) is a showcase example for entropic allostery. For full activation and DNA binding, the homodimeric protein requires the binding of two cyclic AMP (cAMP) molecules in an anti-cooperative manner, the source of which appears to be largely of entropic nature according to previous experimental studies. We here study at atomic detail the allosteric regulation of CAP with Molecular dynamics (MD) simulations. We recover the experimentally observed entropic penalty for the second cAMP binding event with our recently developed force covariance entropy estimator and reveal allosteric communication pathways with Force Distribution Analyses (FDA). Our observations show that CAP binding results in characteristic changes in the interaction pathways connecting the two cAMP allosteric binding sites with each other, as well as with the DNA binding domains. We identified crucial relays in the mostly symmetric allosteric activation network, and suggest point mutants to test this mechanism. Our study suggests inter-residue forces, as opposed to coordinates, as a highly sensitive measure for structural adaptations that, even though minute, can very effectively propagate allosteric signals.
- Subjects :
- Entropy
Escherichia coli Proteins chemistry
Escherichia coli Proteins metabolism
Molecular Dynamics Simulation
Nuclear Magnetic Resonance, Biomolecular
Principal Component Analysis
Protein Binding
Allosteric Site
Cyclic AMP Receptor Protein chemistry
Cyclic AMP Receptor Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7358
- Volume :
- 11
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PLoS computational biology
- Publication Type :
- Academic Journal
- Accession number :
- 26244893
- Full Text :
- https://doi.org/10.1371/journal.pcbi.1004358