2024-03-29T08:37:13Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00018535
2023-01-16T04:07:18Z
320:321:322
Statistical mechanics of protein allostery: Roles of backbone and side-chain structural fluctuations
Itoh, Kazuhito
Sasai, Masaki
open access
© 2011 American Institute of Physics
A statistical mechanical model of allosteric transition of proteins is developed by extending the structure-basedmodel of protein folding to cases that a protein has two different native conformations. Partition function is calculated exactly within the model and free-energysurfaces associated with allostery are derived. In this paper, the model of allosteric transition proposed in a previous paper [Proc. Natl. Acad. Sci. U.S.A134, 7775 (2010)] is reformulated to describe both fluctuation in side-chain configurations and that in backbone structures in a balanced way. The model is applied to example proteins, Ras, calmodulin, and CheY: Ras undergoes the allosteric transition between guanosine diphosphate (GDP)-bound and guanosine triphosphate (GTP)-bound forms, and the model results show that the GDP-bound form is stabilized enough to prevent unnecessary signal transmission, but the conformation in the GTP-bound state bears large fluctuation in side-chain configurations, which may help to bind multiple target proteins for multiple pathways of signaling. The calculated results of calmodulin show the scenario of sequential ordering in Ca^2+ binding and the associated allosteric conformational change, which are realized though the sequential appearing of pre-existing structural fluctuations, i.e., fluctuations to show structures suitable to bind Ca^2+ before its binding. Here, the pre-existing fluctuations to accept the second and third Ca^2+ ions are dominated by the side-chain fluctuation. In CheY, the calculated side-chain fluctuation of Tyr106 is coordinated with the backbone structural change in the β4–α4 loop, which explains the pre-existing Y–T coupling process in this protein. Ability of the model to explain allosteric transitions of example proteins supports the view that the large entropic effects lower the free-energy barrier of allosteric transition.
AIP
2011-03
eng
journal article
AM
http://hdl.handle.net/2237/20621
https://nagoya.repo.nii.ac.jp/records/18535
https://doi.org/10.1063/1.3565025
0021-9606
The Journal of Chemical Physics
134
12
125102
125102
https://nagoya.repo.nii.ac.jp/record/18535/files/ItohSasaiJCP2011.pdf
application/pdf
3.0 MB
2018-02-21