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Title: Native state volume fluctuations in proteins as a mechanism for dynamic allostery

Abstract

Allostery enables tight regulation of protein function in the cellular environment. While existing models of allostery are firmly rooted in the current structure-function paradigm, the mechanistic basis for allostery in the absence of structural change remains unclear. In this study, we show that a typical globular protein is able to undergo significant changes in volume under native conditions while exhibiting no additional changes in protein structure. These native state volume fluctuations were found to correlate with changes in internal motions that were previously recognized as a source of allosteric entropy. This finding offers a novel mechanistic basis for allostery in the absence of canonical structural change. As a result, the unexpected observation that function can be derived from expanded, low density protein states has broad implications for our understanding of allostery and suggests that the general concept of the native state be expanded to allow for more variable physical dimensions with looser packing.

Authors:
 [1];  [2];  [3];  [4]; ORCiD logo [3]
  1. Univ. of Washington, Seattle, WA (United States)
  2. Univ. of North Carolina, Chapel Hill, NC (United States)
  3. Univ. of Alabama, Birmingham, AL (United States)
  4. Argonne National Lab. (ANL), Argonne, IL (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1373407
Grant/Contract Number:
AC02-06CH11357
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of the American Chemical Society
Additional Journal Information:
Journal Volume: 139; Journal Issue: 10; Journal ID: ISSN 0002-7863
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; allostery; SAXS

Citation Formats

Law, Anthony B., Sapienza, Paul J., Zhang, Jun, Zuo, Xiaobing, and Petit, Chad M. Native state volume fluctuations in proteins as a mechanism for dynamic allostery. United States: N. p., 2017. Web. doi:10.1021/jacs.6b12058.
Law, Anthony B., Sapienza, Paul J., Zhang, Jun, Zuo, Xiaobing, & Petit, Chad M. Native state volume fluctuations in proteins as a mechanism for dynamic allostery. United States. doi:10.1021/jacs.6b12058.
Law, Anthony B., Sapienza, Paul J., Zhang, Jun, Zuo, Xiaobing, and Petit, Chad M. Tue . "Native state volume fluctuations in proteins as a mechanism for dynamic allostery". United States. doi:10.1021/jacs.6b12058. https://www.osti.gov/servlets/purl/1373407.
@article{osti_1373407,
title = {Native state volume fluctuations in proteins as a mechanism for dynamic allostery},
author = {Law, Anthony B. and Sapienza, Paul J. and Zhang, Jun and Zuo, Xiaobing and Petit, Chad M.},
abstractNote = {Allostery enables tight regulation of protein function in the cellular environment. While existing models of allostery are firmly rooted in the current structure-function paradigm, the mechanistic basis for allostery in the absence of structural change remains unclear. In this study, we show that a typical globular protein is able to undergo significant changes in volume under native conditions while exhibiting no additional changes in protein structure. These native state volume fluctuations were found to correlate with changes in internal motions that were previously recognized as a source of allosteric entropy. This finding offers a novel mechanistic basis for allostery in the absence of canonical structural change. As a result, the unexpected observation that function can be derived from expanded, low density protein states has broad implications for our understanding of allostery and suggests that the general concept of the native state be expanded to allow for more variable physical dimensions with looser packing.},
doi = {10.1021/jacs.6b12058},
journal = {Journal of the American Chemical Society},
number = 10,
volume = 139,
place = {United States},
year = {Tue Jan 17 00:00:00 EST 2017},
month = {Tue Jan 17 00:00:00 EST 2017}
}

Journal Article:
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Citation Metrics:
Cited by: 10works
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