Zhao Yurong, Deng Li, Wang Jiqian, Xu Hai, Lu Jian R
Centre for Bioengineering and Biotechnology, China University of Petroleum (East China) , 66 Changjiang West Road, Qingdao 266580, China.
Biological Physics Group, School of Physics and Astronomy, The University of Manchester , Manchester M13 9PL, United Kingdom.
Langmuir. 2015 Dec 1;31(47):12975-83. doi: 10.1021/acs.langmuir.5b02303. Epub 2015 Nov 16.
The structural modulation of peptide and protein assemblies under well-controlled conditions is of both fundamental and practical significance. In spite of extensive studies, it remains hugely challenging to tune the self-assembled nanostructures in a controllable manner because the self-assembly processes are dictated by various noncovalent interactions and their interplay. We report here how to manipulate the self-assembly of a designed, symmetric amphiphilic peptide (KI4K) via the solvent-controlled structural transition. Structural transition processes were carefully followed by the combination of transmission electronic microscopy (TEM), atomic force microscopy (AFM), circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR), and small angle neutron scattering (SANS). The results show that the introduction of acetonitrile into water significantly affected the hydrophobic interactions among hydrophobic side chains while imposing little impact on the β-sheet hydrogen bonding between peptide backbones. A structural transition occurred from nanotubes to helical/twisted ribbons and then to thin fibrils with the addition of acetonitrile due to the reduced hydrophobic interactions and the consequent weakening of the lateral stacking between KI4K β-sheets. The increased intermolecular electrostatic repulsions among lysine side chain amino groups had little effect on the lateral stacking of KI4K β-sheets due to the molecular symmetry. Complementary molecular dynamic (MD) simulations also indicated the solvation of acetonitrile molecules into the hydrophobic domains weakening the coherence between the neighboring sheets.
在可控条件下对肽和蛋白质组装体进行结构调控具有重要的基础意义和实际意义。尽管已经进行了广泛的研究，但以可控方式调节自组装纳米结构仍然极具挑战性，因为自组装过程由各种非共价相互作用及其相互作用所决定。我们在此报告如何通过溶剂控制的结构转变来操纵一种设计的对称两亲性肽（KI4K）的自组装。通过透射电子显微镜（TEM）、原子力显微镜（AFM）、圆二色性（CD）、傅里叶变换红外光谱（FTIR）和小角中子散射（SANS）相结合的方法，仔细跟踪结构转变过程。结果表明，向水中引入乙腈会显著影响疏水侧链之间的疏水相互作用，而对肽主链之间的β-折叠氢键影响较小。由于疏水相互作用减弱以及随之而来的KI4Kβ-折叠之间侧向堆积的减弱，随着乙腈的加入，结构发生了从纳米管到螺旋/扭曲带，再到细纤维的转变。由于分子对称性，赖氨酸侧链氨基之间分子间静电排斥力的增加对KI4Kβ-折叠的侧向堆积影响较小。互补的分子动力学（MD）模拟也表明，乙腈分子溶剂化进入疏水区域会削弱相邻片层之间的连贯性。
