Small heat shock proteins (sHsps) constitute a diverse chaperone family that shares the α-crystallin domain, which is flanked by variable, disordered N- and C-terminal extensions. sHsps act as the first line of cellular defense against protein unfolding stress. They form dynamic, large oligomers that represent inactive storage forms. Stress conditions cause a rapid increase in cellular sHsp levels and trigger conformational rearrangements, resulting in exposure of substrate-binding sites and sHsp activation. sHsps bind to early-unfolding intermediates of misfolding proteins in an ATP-independent manner and sequester them in sHsp/substrate complexes. Sequestration protects substrates from further uncontrolled aggregation and facilitates their refolding by ATP-dependent Hsp70-Hsp100 disaggregases. Some sHsps with particularly strong sequestrase activity, such as yeast Hsp42, are critical factors for forming large, microscopically visible deposition sites of misfolded proteins in vivo. These sites are organizing centers for triaging substrates to distinct quality control pathways, preferentially Hsp70-dependent refolding and selective autophagy.

中文翻译：

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小型热激蛋白的细胞功能和作用机理。

小型热激蛋白（sHsps）构成了一个多样化的分子伴侣家族，共有一个α-晶状蛋白结构域，该结构域两侧是可变的，无序的N和C端延伸。sHsps充当了针对蛋白质展开应激的细胞防御的第一道防线。它们形成动态的，大的低聚物，代表不活跃的存储形式。应激条件会导致细胞sHsp水平快速升高并触发构象重排，从而导致底物结合位点暴露和sHsp激活。sHsps以不依赖ATP的方式与错误折叠蛋白的早期折叠中间体结合，并将其隔离在sHsp /底物复合物中。螯合保护底物免受进一步不受控制的聚集，并通过依赖ATP的Hsp70-Hsp100分解油脂促进底物的重折叠。一些具有特别强的螯合酶活性的sHsps，例如酵母Hsp42，是在体内形成折叠错误的蛋白质的大的，在显微镜下可见的沉积位点的关键因素。这些站点是组织中心，用于将底物分类到不同的质量控制途径，优选Hsp70依赖性重折叠和选择性自噬。