This is a short paper on new ways to think about the structure and function of small heat shock proteins (sHSPs), perhaps the most enigmatic family among protein chaperones. The goal is to incorporate new observations regarding the disordered regions of small heat shock proteins (sHSPs) into the large body of structural information on the conserved structural alpha-crystallin domains (ACD) that define the sHSP family. Disordered regions (N-terminal region and C-terminal region or NTR and CTR, respectively) represent over 50% of the sHSP sequence space in the human genome and are refractory to traditional structural biology approaches, posing a roadblock on the path towards a mechanistic understanding of how sHSPs function. A model in which an ACD dimer serves as a template that presents three grooves into which other proteins or other segments of sHSPs can bind is presented. Short segments within the disordered regions are observed to bind into the ACD grooves. There are more binding segments than there are grooves, and each binding event is weak and transient, creating a dynamic equilibrium of tethered and untethered disordered regions. The ability of an NTR to be in dynamic equilibrium between tethered/sequestered and untethered states suggests several mechanistic alternatives that need not be mutually exclusive. New ways of thinking about (and approaching) the intrinsic properties of sHSPs may finally allow the veil of enigma to be removed from sHSPs.

中文翻译：

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揭开谜团的面纱：对小热休克蛋白结构和功能的新见解。


这是一篇关于思考小热休克蛋白 (sHSP) 结构和功能的新方法的简短论文，小热休克蛋白可能是蛋白质伴侣中最神秘的家族。目标是将小热休克蛋白 (sHSP) 无序区域的新观察结果纳入到定义 sHSP 家族的保守结构 α-晶状体蛋白结构域 (ACD) 的大量结构信息中。无序区域（N端区域和C端区域，分别称为NTR和CTR）代表了人类基因组中超过50%的sHSP序列空间，并且难以用传统的结构生物学方法来解决，这给机械化的道路上设置了障碍。了解 sHSP 的功能。提出了一个模型，其中 ACD 二聚体作为模板，呈现三个凹槽，其他蛋白质或 sHSP 的其他片段可以结合到其中。观察到无序区域内的短片段结合到 ACD 凹槽中。结合片段的数量多于凹槽的数量，并且每个结合事件都是弱且短暂的，从而形成了受束缚和不受束缚的无序区域的动态平衡。 NTR 在束缚/隔离和自由状态之间保持动态平衡的能力表明了几种不必相互排斥的机械替代方案。思考（和接近）sHSP 内在特性的新方法可能最终能够揭开 sHSP 的神秘面纱。