Hochberg Georg K A, Benesch Justin L P
Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QZ, United Kingdom.
Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QZ, United Kingdom.
Prog Biophys Mol Biol. 2014 Jul;115(1):11-20. doi: 10.1016/j.pbiomolbio.2014.03.003. Epub 2014 Mar 24.
The human small heat-shock protein αB-crystallin is an extremely difficult molecule to study, with its inherent structural dynamics posing unique challenges to all biophysical and structural biology techniques. Here we highlight how the polydispersity and quaternary dynamics of αB-crystallin are intrinsically inter-twined, and how this can impact on measurements of the oligomeric distribution. We show that, in spite of these difficulties, considerable understanding of the varied fluctuations αB-crystallin undergoes at equilibrium has emerged in the last few years. By reporting on data obtained from a variety of biophysical techniques, we demonstrate how the αB-crystallin solution ensemble is governed by molecular motions of varying amplitude and time-scales spanning several orders of magnitude. We describe how these diverse measurements are being used to construct an integrated view of the dynamical structure of αB-crystallin, and highlight areas that require further interrogation. With its study motivating the refinement of experimental techniques, and the development of new approaches to combine the hybrid datasets, we conclude that αB-crystallin continues to represent a paradigm for dynamical biology.
人类小热休克蛋白αB-晶状体蛋白是一种极难研究的分子，其固有的结构动力学给所有生物物理和结构生物学技术带来了独特挑战。在此，我们强调αB-晶状体蛋白的多分散性和四级动力学如何内在地相互交织，以及这如何影响寡聚体分布的测量。我们表明，尽管存在这些困难，但在过去几年中，人们对αB-晶状体蛋白在平衡状态下经历的各种波动已有了相当深入的了解。通过报告从各种生物物理技术获得的数据，我们展示了αB-晶状体蛋白溶液系综是如何由跨越几个数量级的不同幅度和时间尺度的分子运动所支配的。我们描述了这些不同的测量如何被用于构建αB-晶状体蛋白动态结构的综合视图，并突出了需要进一步探究的领域。随着对它的研究推动了实验技术的完善以及结合混合数据集新方法的发展，我们得出结论，αB-晶状体蛋白仍然是动态生物学的一个范例。
