Polyproline II conformation is one of many local conformational states and is not an overall conformation of unfolded peptides and proteins
Polyproline II conformation is one of many local conformational states and is not an overall conformation of unfolded peptides and proteins
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DOI：
10.1073/pnas.0510549103
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发表时间：
2006-02-07
影响因子：
11.1
通讯作者：
Scheraga, HA
中科院分区：
文献类型：
--
作者：
Makowska, J;Rodziewicz-Motowidlo, S;Scheraga, HA
基于丙氨酸的肽Ac-XX(A)(7)OO-NH2，被称为XAO（其中X， A和0分别表示二氨基丁酸，丙氨酸和鸟氨酸），最近被提出在低温下具有明确的聚脯氨酸II （P-II）构象。根据广泛的NMR和CID研究结果结合理论计算，我们提出的证据表明，相反，该肽没有任何显著数量的有组织的P-II结构，而是存在于N端和c端区域扭曲弯曲的构象集合中。该构象系系通过分子动力学/模拟退火计算，利用AMBER程序，分别从旋转框架核Overhauser效应（ROE）体积和相邻耦合常数3J（HNH α）中得到时间平均距离和二面角约束。计算的旋合平均半径R-g（7.4 +/- 1.0）埃与小角x射线散射（SAXS）测量的结果非常吻合，而如果XAO肽处于Pi，构象，Rg为11.6埃。根据pH、多肽浓度和温度的不同，XAO的CID光谱在217 nm区域具有或不具有最大的正椭圆率，这是P-II结构的特征，反映了一种移位的构象平衡，而不是全或无的转变。因此，“P-II构象”应该被认为是肽和蛋白质中单个氨基酸残基的可接近构象状态之一，而不是折叠早期大多数链的结构。
The alanine-based peptide Ac-XX(A)(7)OO-NH2, referred to as XAO (where X, A, and 0 denote diaminobutyric acid, alanine, and ornithine, respectively), has recently been proposed to possess a well defined polyproline II (P-II) conformation at low temperatures. Based on the results of extensive NMR and CID investigations combined with theoretical calculations, reported here, we present evidence that, on the contrary, this peptide does not have any significant amount of organized P-II structure but exists in an ensemble of conformations with a distorted bend in the N- and C-terminal regions. The conformational ensemble was obtained by molecular dynamics/simulated annealing calculations using the AMBER suite of programs with time-averaged distance and dihedral-angle restraints obtained from rotating-frame nuclear Overhauser effect (ROE) volumes and vicinal coupling constants 3J(HNH alpha), respectively. The computed ensemble-averaged radius of gyration R-g (7.4 +/- 1.0) angstrom is in excellent agreement with that measured by small-angle x-ray scattering (SAXS) whereas, if the XAO peptide were in the Pi, conformation, Rg would be 11.6 angstrom. Depending on the pH, peptide concentration, and temperature, the CID spectra of XAO do or do not possess the maximum with positive ellipticity in the 217-nm region, which is characteristic of the P-II structure, reflecting a shifting conformational equilibrium rather than an all-or-none transition. The "P-II conformation" should, therefore, be considered as one of the accessible conformational states of individual amino acid residues in peptides and proteins rather than as a structure of most of the chain in the early stage of folding.