Evolutionally conserved intermediates between ubiquitin and NEDD8
Evolutionally conserved intermediates between ubiquitin and NEDD8
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DOI：
10.1016/j.jmb.2006.07.074
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发表时间：
2006-10-20
影响因子：
5.6
通讯作者：
Akasaka, Kazuyuki
中科院分区：
文献类型：
--
作者：
Kitahara, Ryo;Yamaguchi, Yoshiki;Akasaka, Kazuyuki
对共同结构基序的研究提供了关于为什么蛋白质保守相似的拓扑结构但可能具有非保守氨基酸序列的额外信息。包含泛素超折叠的蛋白质具有相似的拓扑结构，尽管序列保守性相当差。在这里，我们提出了新的相似性和差异蛋白质泛素和NEDD 8。它们具有57%的序列相同性，几乎相同的骨架拓扑结构和相似的功能策略，尽管它们的生理功能相互不同。利用变压核磁共振谱，我们发现这两种蛋白质在进化保守的酶结合区具有相似的构象波动，并含有结构相似的局部无序构象（I）与基本折叠构象（N）处于平衡状态。这两种蛋白质之间的一个显著差异是，NEDD 8的I的平衡群体要大得多。（Δ G（NI）（0）< 5 kJ/mol）（Δ G（NI）（0）=15.2（+/- 1.0）kJ/mol），而且NEDD的整体展开趋势（U）也要高得多8（Δ G（NU）（0）=11.0（+/-1.5）kJ/mol）比对于泛素（Δ G（NU）（0）=31.3（+/-4.7）kJ/mol）。这些结果表明，局部无序构象异构体（1）和整体去折叠构象异构体（U）在热力学稳定性上的显著差异是决定这两种结构相似的蛋白质在生理学上功能差异的关键。(c)2006爱思唯尔有限公司保留所有权利。
The investigation of common structural motifs provides additional information on why proteins conserve similar topologies yet may have non-conserved amino acid sequences. Proteins containing the ubiquitin superfold have similar topologies, although the sequence conservation is rather poor. Here, we present novel similarities and differences between the proteins ubiquitin and NEDD8. They have 57% identical sequence, almost identical backbone topology and similar functional strategy, although their physiological functions are mutually different. Using variable pressure NMR spectroscopy, we found that the two proteins have similar conformational fluctuation in the evolutionary conserved enzyme-binding region and contain a structurally similar locally disordered conformer (I) in equilibrium with the basic folded conformer (N). A notable difference between the two proteins is that the equilibrium population of I is far greater for NEDD8 (Delta G(NI)(0)< 5 kJ/mol) than for ubiquitin (Delta G(NI)(0)=15.2 (+/- 1.0) kJ/mol), and that the tendency for overall unfolding (U) is also far higher for NEDD8 (Delta G(NU)(0)=11.0(+/- 1.5) kJ/mol) than for ubiquitin (Delta G(NU)(0)=31.3(+/- 4.7) kJ/mol). These results suggest that the marked differences in thermodynamic stabilities of the locally disordered conformer (1) and the overall unfolding species (U) are a key to determine the functional differences of the two structurally similar proteins in physiology. (c) 2006 Elsevier Ltd. All rights reserved.