Basic folded and low-populated locally disordered conformers of SUMO-2 characterized by NMR spectroscopy at varying pressures
Basic folded and low-populated locally disordered conformers of SUMO-2 characterized by NMR spectroscopy at varying pressures
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DOI：
10.1021/bi7014458
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发表时间：
2008-01-08
期刊：
影响因子：
2.9
通讯作者：
Akasaka, Kazuyuki
中科院分区：
文献类型：
--
作者：
Kitahara, Ryo;Zhao, Chenhua;Akasaka, Kazuyuki
SUMO蛋白是一组翻译后泛素样修饰物，与其他泛素样修饰物一样，具有靶酶（E1和E2），例如，泛素和NEDD 8，但它们的生理作用是完全不同的。为了确定泛素样修饰物的特征性分子设计，。我们已经分别利用标准和变压NMR光谱研究了溶液中人SUMO-2的结构，不仅在其基本折叠状态下，而且在其较高能量状态下。我们已经确定了平均坐标的基本折叠构象在环境压力下，这给出了一个骨架结构几乎相同的泛素和NEDD 8。我们已经进一步研究了构象波动在一个广泛的构象空间，使用变压NMR光谱在30-3 kbar的范围内，通过它，我们发现一个低人口（类似于2.5%）的替代构象优先无序的酶结合段。替代构象是结构上非常接近，但明显不同的平衡人口从那些泛素和NEDD 8。这些结果支持了我们的观点，即翻译后泛蛋白样修饰剂是经过进化设计的，在其低密度、高能量的构象中而不是在其基本折叠的构象中在结构和热力学上发挥作用。
SUMO proteins, a group of post-translational ubiquitin-like modifiers, have target enzymes (E1 and E2) like other ubiquitin-like modifiers, e.g., ubiquitin and NEDD8, but their physiological roles are quite different. In an effort to determine the characteristic molecular design of ubiquitin-like modifiers,. we have investigated the structure of human SUMO-2 in solution not only in its basic folded state but also in its higher-energy state by utilizing standard and variable-pressure NMR spectroscopy, respectively. We have determined average coordinates of the basic folded conformer at ambient pressure, which gives a backbone structure almost identical with those of ubiquitin and NEDD8. We have further investigated conformational fluctuations in a wide conformational space using variable-pressure NMR spectroscopy in the range of 30-3 kbar, by which we find a low-populated ( similar to 2.5%) alternative conformer preferentially disordered in the enzyme-binding segment. The alternative conformer is structurally very close to but markedly different in equilibrium population from those for ubiquitin and NEDD8. These results support our notion that post-translational ubiquitin-like modifiers are evolutionarily designed for function both structurally and thermodynamically in their low-populated, high-energy conformers rather than in their basic folded conformers.