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. Although 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. 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.affiliation: Department of Otolaryngology - Head and Neck Surgery, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Law
authors.affiliation: Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Sapienza
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: X-ray Science Division, Argonne National Laboratory , Argonne, Illinois 60439, United States.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
authors.forename: Chad M
authors.identifier: 0000-0003-4933-6245
authors.initials: CM
authors.lastname: Petit
mesh_terms: D000494:Allosteric Regulation; D019277:Entropy; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011506:Proteins