Laboratory of Molecular Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
Biochemistry. 2012 Jan 17;51(2):643-52. doi: 10.1021/bi201494h. Epub 2012 Jan 6.
The temperature dependence of dynamic parameters derived from nuclear magnetic resonance (NMR) relaxation data is related to conformational entropy of the system under study. This provides information such as macromolecules stability and thermodynamics of ligand binding. We studied the temperature dependence of NMR order parameter of glutamine binding protein (GlnBP), a periplasmic binding protein (PBP) highly specific to L-glutamine associated with its ABC transporter, with the goal of elucidating the dynamical differences between the respective ligand bound and free forms. We found that the protein-ligand interaction, which is stabilized at higher temperature, has a striking effect on the stability of the hydrophobic core of the large domain of GlnBP. Moreover, in contrast to what was found for less specific PBPs, the decreasing backbone motion of the hinge region at increasing temperature supports the idea that the likelihood that GlnBP can adopt a ligand free closed conformation in solution diminishes at higher temperatures. Our results support the induced-fit model as mode of action for GlnBP. In addition, we found that the backbones of residues involved in a salt bridge do not necessarily become more rigid as the temperature rises as it was previously suggested [Vinther, J. M., et al. (2011) J. Am. Chem. Soc., 133, 271-278]. Our results show that for this to happen these residues have to also directly interact with a region of the protein that is becoming more rigid as the temperature increases.
从核磁共振(NMR)弛豫数据得出的动态参数的温度依赖性与研究体系的构象熵有关。这提供了诸如大分子稳定性和配体结合热力学等信息。我们研究了与 ABC 转运体相关的谷氨酸结合蛋白(GlnBP)的 NMR 序参数的温度依赖性,GlnBP 是一种高度特异的 L-谷氨酸外周结合蛋白,旨在阐明各自配体结合和游离形式之间的动力学差异。我们发现,在较高温度下稳定的蛋白质-配体相互作用对 GlnBP 大亚基的疏水区的稳定性有显著影响。此外,与特异性较低的 PBPs 相反,随着温度的升高,铰链区域的后骨架运动减少,这支持了 GlnBP 在溶液中可以采取无配体的封闭构象的可能性在较高温度下降低的观点。我们的结果支持诱导契合模型作为 GlnBP 的作用模式。此外,我们发现,如前所述,参与盐桥的残基的骨架并不一定随着温度的升高而变得更加刚性[Vinther, J. M., 等人。(2011)J. Am. Chem. Soc.,133, 271-278]。我们的结果表明,要使这种情况发生,这些残基还必须直接与蛋白质的一个区域相互作用,随着温度的升高,该区域变得更加刚性。