Chandrashekar Indu R, Cowsik Sudha M
School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067, India.
Biophys J. 2003 Dec;85(6):4002-11. doi: 10.1016/S0006-3495(03)74814-0.
The solution structure of NKA, a decapeptide of mammalian origin, has been characterized by CD spectropolarimetry and 2D proton nuclear magnetic resonance (2D 1H-NMR) spectroscopy in both aqueous and membrane mimetic solvents. Unambiguous NMR assignments of protons have been made with the aid of correlation spectroscopy (DQF-COSY and TOCSY) experiments and nuclear Overhauser effect spectroscopy (NOESY and ROESY) experiments. The distance constraints obtained from the NMR data have been utilized to generate a family of structures, which have been refined using restrained energy minimization and dynamics. These data show that in water NKA prefers to be in an extended chain conformation whereas a helical conformation is induced in the central core and the C-terminal region (D4-M10) of the peptide in the presence of perdeuterated dodecylphosphocholine (DPC) micelles, a membrane model system. Though less defined the N-terminus also displays some degree of order and a possible turn structure. The conformation adopted by NKA in the presence of DPC micelles represents a structural motif typical of neurokinin-2 selective agonists and is similar to that reported for eledoisin in hydrophobic environment.
NKA是一种源自哺乳动物的十肽，其溶液结构已通过圆二色光谱偏振法以及二维质子核磁共振（2D 1H-NMR）光谱法在水性溶剂和模拟膜溶剂中进行了表征。借助相关光谱实验（双量子滤波相关谱（DQF-COSY）和全相关谱（TOCSY））以及核Overhauser效应光谱实验（核Overhauser效应谱（NOESY）和旋转框架核Overhauser效应谱（ROESY））对质子进行了明确的核磁共振归属。从核磁共振数据获得的距离限制已用于生成一系列结构，并使用受限能量最小化和动力学对其进行了优化。这些数据表明，在水中NKA倾向于呈伸展链构象，而在存在全氘代十二烷基磷酸胆碱（DPC）胶束（一种膜模型系统）的情况下，该肽的中央核心和C末端区域（D4-M10）会诱导形成螺旋构象。尽管N末端的定义不太明确，但也显示出一定程度的有序性和可能的转角结构。NKA在DPC胶束存在下所采用的构象代表了神经激肽-2选择性激动剂典型的结构基序，并且与在疏水环境中报道的eledoisin的构象相似。
