Intrinsic protein disorder could be overlooked in cocrystallization conditions: An SRCD case study
Intrinsic protein disorder could be overlooked in cocrystallization conditions: An SRCD case study
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DOI：
10.1002/pro.3010
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发表时间：
2016-11-01
期刊：
影响因子：
8
通讯作者：
Gyurcsik, Bela
中科院分区：
文献类型：
--
作者：
Nemeth, Eszter;Balogh, Ria K.;Gyurcsik, Bela
X射线衍射法在蛋白质研究中占主导地位，因为它可以提供这些不同大分子或其分子复合物与相互作用伙伴的3D结构：底物，抑制剂和/或辅因子。在这里，我们表明，在共结晶条件下的结果可以反映诱导蛋白质折叠，而不是（部分）无序的原始结构。同步辐射圆二色光谱的分析表明，Im 7免疫蛋白通过复合物的形成稳定了未折叠的NColE 7核酸酶突变体的天然样溶液结构。这与以下事实一致：在具有其抑制剂或底物的几种可用晶体结构中，所有NCol E7结构几乎相同。我们的研究结果提请注意蛋白质修饰的可能结构后果，这往往是隐藏的补偿效应的分子间相互作用。因此，越来越多的证据表明蛋白质内在紊乱的重要性，需要更广泛的补充实验，在溶液相中与未连接形式的蛋白质的兴趣。
X-ray diffractometry dominates protein studies, as it can provide 3D structures of these diverse macromolecules or their molecular complexes with interacting partners: substrates, inhibitors, and/ or cofactors. Here, we show that under cocrystallization conditions the results could reflect induced protein folds instead of the (partially) disordered original structures. The analysis of synchrotron radiation circular dichroism spectra revealed that the Im7 immunity protein stabilizes the native-like solution structure of unfolded NColE7 nuclease mutants via complex formation. This is consistent with the fact that among the several available crystal structures with its inhibitor or substrate, all NColE7 structures are virtually the same. Our results draw attention to the possible structural consequence of protein modifications, which is often hidden by compensational effects of intermolecular interactions. The growing evidence on the importance of protein intrinsic disorder thus, demands more extensive complementary experiments in solution phase with the unligated form of the protein of interest.