Sequence-Specific Random Coil Chemical Shifts of Intrinsically Disordered Proteins
Sequence-Specific Random Coil Chemical Shifts of Intrinsically Disordered Proteins
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DOI：
10.1021/ja105656t
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发表时间：
2010-12-29
影响因子：
15
通讯作者：
Mulder, Frans A. A.
中科院分区：
文献类型：
--
作者：
Tamiola, Kamil;Acar, Burcin;Mulder, Frans A. A.
虽然内在无序蛋白（IDPs）广泛存在于自然界中，并在生物学中发挥着多种重要作用，但迄今为止它们的结构特征很少。幸运的是，利用核磁共振光谱的强化努力已经开始揭示它们构象景观的广度。特别是，多肽主链的化学位移正在成为从“随机线圈”状态向规范类型二级结构的局部动态偏差的有力描述符。这些偏离，反过来，可以连接到功能或功能失调的蛋白质状态，例如，在适应性分子识别和蛋白质聚集。在这里，我们描述了IDP主链N-15、H-1(N) H-1（α）、C-13(O)、C-13（β）和C-13（α）化学位移的第一个清单，使用了一组14个序列和功能不相关的蛋白质的数据。采用奇异值分解方法，根据20个氨基酸特异性随机螺旋化学位移和40个序列依赖的左邻和右邻校正因子，对6903个测量位移进行了参数化，建立了ncIDP库。对于天然未折叠的蛋白质，从初级序列计算的随机线圈主链化学位移与实验测量的N-15、H-1(N)、H-1（α）、C-13(O)、C-13（β）和C-13（α）化学位移的均方根偏差分别为0.65、0.14、0.12、0.50、0.36和0.41 ppm。ncIDP预测精度明显高于小肽或折叠蛋白“线圈”区域的文库。
Although intrinsically disordered proteins (IDPs) are widespread in nature and play diverse and important roles in biology, they have to date been little characterized structurally. Auspiciously, intensified efforts using NMR spectroscopy have started to uncover the breadth of their conformational landscape. In particular, polypeptide backbone chemical shifts are emerging as powerful descriptors of local dynamic deviations from the "random coil" state toward canonical types of secondary structure. These digressions, in turn, can be connected to functional or dysfunctional protein states, for example, in adaptive molecular recognition and protein aggregation. Here we describe a first inventory of IDP backbone N-15, H-1(N) H-1(alpha), C-13(O), C-13(beta) and C-13(alpha) chemical shifts using data obtained for a set of 14 proteins of unrelated sequence and function. Singular value decomposition was used to parametrize this database of 6903 measured shifts collectively in terms of 20 amino acid-specific random coil chemical shifts and 40 sequence-dependent left- and right-neighbor correction factors, affording the ncIDP library. For natively unfolded proteins, random coil backbone chemical shifts computed from the primary sequence displayed root-mean-square deviations of 0.65, 0.14, 0.12, 0.50, 0.36, and 0.41 ppm from the experimentally measured values for the N-15, H-1(N), H-1(alpha), C-13(O), C-13(beta), and C-13(alpha) chemical shifts, respectively. The ncIDP prediction accuracy is significantly higher than that obtained with libraries for small peptides or "coil" regions of folded proteins.