
Driving protein conformational cycles in physiology and disease: “Frustrated” amino acid interaction networks define dynamic energy landscapes
We propose a general framework by which dynamic interactions within a protein will promote the necessary series of structural changes, or “conformational cycle”, required for function. We suggest that the free energy landscape of a protein is biased towards this conformational cycle. Fluctuations into higher energy, albeit thermally accessible, conformations drive the conformational cycle forward. The amino acid interaction network is defined as those intra-protein interactions that contribute most to the free energy landscape. Some network connections are consistent in every structural state, while others periodically change their interaction strength according to the conformational cycle. As we review here, structural transitions change these periodic network connections, which then predisposes the protein towards the next set of network changes, and hence the next structural change. These concepts are illustrated by our recent work on tryptophan synthase. Disruption of these dynamic connections may lead to aberrant protein function and disease states.
This is the peer reviewed version of the following article: [D’Amico, R.N., Murray, A.M., and Boehr, D.D. (2020). Driving Protein Conformational Cycles in Physiology and Disease: “Frustrated” Amino Acid Interaction Networks Define Dynamic Energy Landscapes. BioEssays 42, 2000092.], which has been published in final form at https://doi.org/10.1002/bies.202000092. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions: https://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.html#3.
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Work Title | Driving protein conformational cycles in physiology and disease: “Frustrated” amino acid interaction networks define dynamic energy landscapes |
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License | In Copyright (Rights Reserved) |
Work Type | Article |
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Publication Date | July 27, 2020 |
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Deposited | February 24, 2021 |
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