ArticleProceedings of the National Academy of Sciences of the United States of America2008
Entropic contributions and the influence of the hydrophobic environment in promiscuous protein-protein association.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
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- Cryo-EM analysis of Pseudomonas phage Pa193 structural components.Communications biology · 2024Article
- Cryo-EM analysis of Pseudomonas phage Pa193 structural components.Research square · 2024Article
- Developing end-point methods for absolute binding free energy calculation using the Boltzmann-quasiharmonic model.Physical chemistry chemical physics : PCCP · 2022Article
- Exploring the Free-Energy Landscape and Thermodynamics of Protein-Protein Association.Biophysical journal · 2020Article
- The Plasma Factor XIII Heterotetrameric Complex Structure: Unexpected Unequal Pairing within a Symmetric Complex.Biomolecules · 2019Article
- Binding Thermodynamics and Kinetics Calculations Using Chemical Host and Guest: A Comprehensive Picture of Molecular Recognition.Journal of chemical theory and computation · 2018Article
- Thermodynamic Basis of Selectivity in the Interactions of Tissue Inhibitors of Metalloproteinases N-domains with Matrix Metalloproteinases-1, -3, and -14.The Journal of biological chemistry · 2016Article
- Dissociation of a Dynamic Protein Complex Studied by All-Atom Molecular Simulations.Biophysical journal · 2016Article
- Matched Peptides: Tuning Matched Molecular Pair Analysis for Biopharmaceutical Applications.Journal of chemical information and modeling · 2015Article
- A universal entropy-driven mechanism for thioredoxin-target recognition.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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- Disulfide-mediated stabilization of the IκB kinase binding domain of NF-κB essential modulator (NEMO).Biochemistry · 2014Article
- Dystroglycan binding to α-neurexin competes with neurexophilin-1 and neuroligin in the brain.The Journal of biological chemistry · 2014Article
- Role of β-lactamase residues in a common interface for binding the structurally unrelated inhibitory proteins BLIP and BLIP-II.Protein science : a publication of the Protein Society · 2014Article
- Review
- Structure-affinity properties of a high-affinity ligand of FKBP12 studied by molecular simulations of a binding intermediate.PloS one · 2014Article
- Agonist and antagonist binding to the nuclear vitamin D receptor: dynamics, mutation effects and functional implications.In silico pharmacology · 2013Article
- Binding efficiency of protein-protein complexes.Biochemistry · 2012Article
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Authors and funding
5 authors.
Funding
Abstract
The mechanisms by which a promiscuous protein can strongly interact with several different proteins using the same binding interface are not completely understood. An example is protein kinase A (PKA), which uses a single face on its docking/dimerization domain to interact with multiple A-kinase anchoring proteins (AKAP) that localize it to different parts of the cell. In the current study, the configurational entropy contributions to the binding between the AKAP protein HT31 with the D/D domain of RII alpha-regulatory subunit of PKA were examined. The results show that the majority of configurational entropy loss for the interaction was due to decreased fluctuations within rotamer states of the side chains. The result is in contrast to the widely held approximation that the decrease in the number of rotamer states available to the side chains forms the major component. Further analysis showed that there was a direct linear relationship between total configurational entropy and the number of favorable, alternative contacts available within hydrophobic environments. The hydrophobic binding pocket of the D/D domain provides alternative contact points for the side chains of AKAP peptides that allow them to adopt different binding conformations. The increase in binding conformations provides an increase in binding entropy and hence binding affinity. We infer that a general strategy for a promiscuous protein is to provide alternative contact points at its interface to increase binding affinity while the plasticity required for binding to multiple partners is retained. Implications are discussed for understanding and treating diseases in which promiscuous protein interactions are used.
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