Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
Biochemistry. 2010 Nov 16;49(45):9746-55. doi: 10.1021/bi101000m. Epub 2010 Oct 22.
To date, very few βγ-crystallins have been identified and structurally characterized. Several of them have been shown to bind Ca(2+) and thereby enhance their stability without any significant change in structure. Although Ca(2+)-induced conformational changes have been reported in two putative βγ-crystallins from Caulobacter crescentus and Yersinia pestis, they are shown to be partially unstructured, and whether they acquire a βγ-crystallin fold is not known. We describe here a βγ-crystallin domain, hahellin, its Ca(2+) binding properties and NMR structure. Unlike any other βγ-crystallin, hahellin is characterized as a pre-molten globule (PMG) type of natively unfolded protein domain. It undergoes drastic conformational change and acquires a typical βγ-crystallin fold upon Ca(2+) binding and hence acts as a Ca(2+)-regulated conformational switch. However, it does not bind Mg(2+). The intrinsically disordered Ca(2+)-free state and the close structural similarity of Ca(2+)-bound hahellin to a microbial βγ-crystallin homologue, Protein S, which shows Ca(2+)-dependent stress response, make it a potential candidate for the cellular functions. This study indicates the presence of a new class of natively unfolded βγ-crystallins and therefore the commencement of the possible functional roles of such proteins in this superfamily.
迄今为止，已鉴定出的 βγ-晶体蛋白数量非常少，并且其结构特征也得到了很好的描述。其中一些已经被证明可以结合 Ca(2+)，从而增强其稳定性，而结构没有明显变化。虽然已经报道了来自新月柄杆菌和鼠疫耶尔森菌的两种假定的 βγ-晶体蛋白中的 Ca(2+)-诱导构象变化，但它们显示出部分无结构，并且它们是否获得 βγ-晶体蛋白折叠尚不清楚。我们在这里描述了一个 βγ-晶体蛋白结构域 hahellin 及其 Ca(2+)结合特性和 NMR 结构。与其他任何 βγ-晶体蛋白不同，hahellin 的特征是一种预熔球蛋白 (PMG) 类型的天然无结构蛋白结构域。它在结合 Ca(2+)后经历剧烈的构象变化并获得典型的 βγ-晶体蛋白折叠，因此充当 Ca(2+)调节的构象开关。然而，它不结合 Mg(2+)。无 Ca(2+)的固有无序状态和与微生物 βγ-晶体蛋白同源物 Protein S 的 Ca(2+)-结合态 hahellin 的紧密结构相似性，后者显示出 Ca(2+)-依赖性应激反应，使其成为细胞功能的潜在候选者。这项研究表明存在一类新的天然无结构的 βγ-晶体蛋白，因此这些蛋白质在这个超家族中可能具有功能作用。
