National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
J Mol Biol. 2011 Sep 2;411(5):1037-48. doi: 10.1016/j.jmb.2011.06.044. Epub 2011 Jul 2.
Proteins exist as conformational ensembles composed of multiple interchanging substates separated by kinetic barriers. Interconverting conformations are often difficult to probe, owing to their sparse population and transient nature. Here, we report the identification and characterization of a subset of conformations in ubiquitin that participate in microsecond-to-millisecond motions in the amides of Ile23, Asn25, and Thr55. A novel side chain to the backbone hydrogen bond that regulates these motions has also been identified. Combining our NMR studies with the available X-ray data, we have unearthed the physical process underlying slow motions-the interconversion of a type I into a type II β-turn flip at residues Glu51 through Arg54. Interestingly, the dominant conformer of wild-type ubiquitin observed in solution near neutral pH is only represented by about 22% of the crystal structures. The conformers generated as a result of the dynamics of the hydrogen bond appear to be correlated to ligand recognition by ubiquitin.
蛋白质以由多个相互转换的亚稳态组成的构象集合体存在，这些亚稳态之间被动力学障碍隔开。由于其稀疏的种群和瞬态性质，相互转换的构象通常难以探测。在这里，我们报告了在泛素中鉴定和描述了一组构象，这些构象参与了异亮氨酸 23、天冬酰胺 25 和苏氨酸 55 酰胺的微秒至毫秒运动。还鉴定了一种调节这些运动的新的侧链到骨干氢键。将我们的 NMR 研究与现有的 X 射线数据相结合，我们已经揭示了慢运动的物理过程——残基 Glu51 到 Arg54 的 I 型到 II 型β-转角翻转的相互转换。有趣的是，在接近中性 pH 的溶液中观察到的野生型泛素的主要构象仅代表晶体结构的约 22%。由于氢键的动力学产生的构象似乎与泛素的配体识别相关。
