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蜂毒肽四聚体-单体转变过程中蛋白质(去)折叠的溶剂化作用

Solvation in protein (un)folding of melittin tetramer-monomer transition.

作者信息

Othon Christina M, Kwon Oh-Hoon, Lin Milo M, Zewail Ahmed H

机构信息

Physical Biology Center for Ultrafast Science and Technology, Arthur Amos Noyes Laboratory of Chemical Physics, California Institute of Technology, Pasadena, CA 91125, USA.

出版信息

Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12593-8. doi: 10.1073/pnas.0905967106. Epub 2009 Jul 21.

Abstract

Protein structural integrity and flexibility are intimately tied to solvation. Here, we examine the effect that changes in bulk and local solvent properties have on protein structure and stability. We observe the change in solvation of an unfolding of the protein model, melittin, in the presence of a denaturant, trifluoroethanol. The peptide system displays a well defined transition in that the tetramer unfolds without disrupting the secondary or tertiary structure. In the absence of local structural perturbation, we are able to reveal exclusively the role of solvation dynamics in protein structure stabilization and the (un)folding pathway. A sudden retardation in solvent dynamics, which is coupled to the change in protein structure, is observed at a critical trifluoroethanol concentration. The large amplitude conformational changes are regulated by the local solvent hydrophobicity and bulk solvent viscosity.

摘要

蛋白质的结构完整性和灵活性与溶剂化密切相关。在此,我们研究了整体和局部溶剂性质的变化对蛋白质结构和稳定性的影响。我们观察了在变性剂三氟乙醇存在下,蛋白质模型蜂毒素展开时溶剂化的变化。该肽系统呈现出明确的转变,即四聚体展开而不破坏二级或三级结构。在没有局部结构扰动的情况下,我们能够单独揭示溶剂化动力学在蛋白质结构稳定和(去)折叠途径中的作用。在临界三氟乙醇浓度下,观察到与蛋白质结构变化相关的溶剂动力学突然减慢。大幅度的构象变化受局部溶剂疏水性和整体溶剂粘度的调节。

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