title: Size and sequence and the volume change of protein folding.
abstract: The application of hydrostatic pressure generally leads to protein unfolding, implying, in accordance with Le Chatelier's principle, that the unfolded state has a smaller molar volume than the folded state. However, the origin of the volume change upon unfolding, ΔV(u), has yet to be determined. We have examined systematically the effects of protein size and sequence on the value of ΔV(u) using as a model system a series of deletion variants of the ankyrin repeat domain of the Notch receptor. The results provide strong evidence in support of the notion that the major contributing factor to pressure effects on proteins is their imperfect internal packing in the folded state. These packing defects appear to be specifically localized in the 3D structure, in contrast to the uniformly distributed effects of temperature and denaturants that depend upon hydration of exposed surface area upon unfolding. Given its local nature, the extent to which pressure globally affects protein structure can inform on the degree of cooperativity and long-range coupling intrinsic to the folded state. We also show that the energetics of the protein's conformations can significantly modulate their volumetric properties, providing further insight into protein stability.
authors: Centre de Biochimie Structurale, INSERM U1054, CNRS UMR5048, Université Montpellier 1, Montpellier, France.
authors: Jean-Baptiste
authors: JB
authors: Rouget
authors: Tural
authors: T
authors: Aksel
authors: Julien
authors: J
authors: Roche
authors: Jean-Louis
authors: JL
authors: Saldana
authors: Angel E
authors: AE
authors: Garcia
authors: Doug
authors: D
authors: Barrick
authors: Catherine A
authors: CA
authors: Royer
mesh_terms: D000595:Amino Acid Sequence; D017089:Ankyrin Repeat; D001426:Bacterial Proteins / Q000737:chemistry*; D020607:Halorhodospira halophila / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011489:Protein Denaturation; D017510:Protein Folding; D051880:Receptors, Notch / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D051880:Receptors, Notch