title: Coupled motion in proteins revealed by pressure perturbation.
abstract: The cooperative nature of protein substructure and internal motion is a critical aspect of their functional competence about which little is known experimentally. NMR relaxation is used here to monitor the effects of high pressure on fast internal motion in the protein ubiquitin. In contrast to the main chain, the motions of the methyl-bearing side chains have a large and variable pressure dependence. Within the core, this pressure sensitivity correlates with the magnitude of motion at ambient pressure. Spatial clustering of the dynamic response to applied hydrostatic pressure is also seen, indicating localized cooperativity of motion on the sub-nanosecond time scale and suggesting regions of variable compressibility. These and other features indicate that the native ensemble contains a significant fraction of members with characteristics ascribed to the recently postulated "dry molten globule". The accompanying variable side-chain conformational entropy helps complete our view of the thermodynamic architecture underlying protein stability, folding, and function.
authors.affiliation: Graduate Group in Biochemistry and Molecular Biophysics, Department of Biochemistry & Biophysics, University of Pennsylvania, Philadelphia, 19104, United States.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Fu
authors.forename: Vignesh
authors.initials: V
authors.lastname: Kasinath
authors.forename: Veronica R
authors.initials: VR
authors.lastname: Moorman
authors.forename: Nathaniel V
authors.initials: NV
authors.lastname: Nucci
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Hilser
authors.forename: A Joshua
authors.initials: AJ
authors.lastname: Wand
mesh_terms: D000818:Animals; D002417:Cattle; D019277:Entropy; D006801:Humans; D008958:Models, Molecular; D009038:Motion; D019906:Nuclear Magnetic Resonance, Biomolecular; D011312:Pressure; D011487:Protein Conformation; D055550:Protein Stability; D025801:Ubiquitin / Q000737:chemistry*
chemical_list: D025801:Ubiquitin