An assignment of intrinsically disordered regions of proteins based on NMR structures.
An assignment of intrinsically disordered regions of proteins based on NMR structures.
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DOI：
10.1016/j.jsb.2012.10.017
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发表时间：
2013-01
影响因子：
3
通讯作者：
Fukuchi, Satoshi
中科院分区：
文献类型：
--
作者：
Ota, Motonori;Koike, Ryotaro;Amemiya, Takayuki;Tenno, Takeshi;Romero, Pedro R.;Hiroaki, Hidekazu;Dunker, A. Keith;Fukuchi, Satoshi
关键词：
内源无序蛋白在生理条件下不具有稳定的三维结构，但在生物现象中起着重要作用。在大多数情况下，内在无序表现在IDP的片段或结构域中，称为内在无序区（IDR），但也存在完全无序的IDP。尽管IDR可以作为通过X射线晶体学确定的蛋白质结构中的缺失残基来检测，但是还没有开发出从通过核磁共振（NMR）获得的结构中鉴定IDR的方案。在这里，我们提出了一种计算方法来分配基于NMR结构的IDR。我们比较了丢失的残留物的X射线结构与残留物的NMR结构的偏差相同的蛋白质，并推导出一个阈值偏差，给出了最好的相关性的有序和无序的区域的两种结构。将得到的阈值3.2 μ m应用于其结构仅由NMR确定的蛋白质，并对所得IDR进行分析，并与没有NMR对应物的X射线结构在序列长度、IDR分数、蛋白质功能、细胞位置和氨基酸组成方面进行比较，所有这些都表明了不同的特征。与结构蛋白质相比，对IDP的结构知识仍然不足。我们的方法可以从NMR确定的结构中收集和利用IDR，从而潜在地增强对IDP的理解。
Intrinsically disordered proteins (IDPs) do not adopt stable three-dimensional structures in physiological conditions, yet these proteins play crucial roles in biological phenomena. In most cases, intrinsic disorder manifests itself in segments or domains of an IDP, called intrinsically disordered regions (IDRs), but fully disordered IDPs also exist. Although IDRs can be detected as missing residues in protein structures determined by X-ray crystallography, no protocol has been developed to identify IDRs from structures obtained by Nuclear Magnetic Resonance (NMR). Here, we propose a computational method to assign IDRs based on NMR structures. We compared missing residues of X-ray structures with residue-wise deviations of NMR structures for identical proteins, and derived a threshold deviation that gives the best correlation of ordered and disordered regions of both structures. The obtained threshold of 3.2 Å was applied to proteins whose structures were only determined by NMR, and the resulting IDRs were analyzed and compared to those of X-ray structures with no NMR counterpart in terms of sequence length, IDR fraction, protein function, cellular location, and amino acid composition, all of which suggest distinct characteristics. The structural knowledge of IDPs is still inadequate compared with that of structured proteins. Our method can collect and utilize IDRs from structures determined by NMR, potentially enhancing the understanding of IDPs.
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影响因子：
2.9
作者：
Garbuzynskiy, SO;Melnik, BS;Galzitskaya, OV
通讯作者：
Galzitskaya, OV
DOI：
10.1016/j.bbrc.2007.12.066
发表时间：
2008-02-22
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Sullivan M
影响因子：
2.9
作者：
Dunker, AK;Lawson, JD;Obradovic, Z
通讯作者：
Obradovic, Z
影响因子：
13.8
作者：
Henrick, K;Thornton, JM
通讯作者：
Thornton, JM