Mahato Dhani Ram, Fischer Wolfgang B
Institute of Biophotonics and Biophotonics & Molecular Imaging Research Center (BMIRC), School of Biomedical Science and Engineering, National Yang-Ming University , Taipei 112, Taiwan.
J Phys Chem B. 2016 Dec 29;120(51):13076-13085. doi: 10.1021/acs.jpcb.6b10050. Epub 2016 Dec 15.
Protein E5 is a polytopic 83 amino acid membrane protein with three transmembrane domains (TMDs), encoded by high-risk human papillomavirus-16 (HPV-16). HPV-16 is found to be the causative agent for cervical cancer. Protein E5, among other proteins (e.g., E6, E7), is expressed at an "early" (E) stage when the cell turns malignant. It has been experimentally found that E5 forms hexameric assemblies, which show the characteristics of the class of so-called channel-forming proteins by rendering lipid membranes permeable to ions and small molecules. Protein E5 is used to achieve structural models of the protein in assembled bundles using a force field-based docking approach. Extended molecular dynamics simulations of selected bundles in fully hydrated lipid bilayers suggest the second TMD to be pore-lining, allowing for water columns to exist within the lumen of the pore. Full correlation analysis indicates asymmetric dynamics within the monomers of the bundle. Potential of mean force calculations of a snapshot structure of the putative open pore of the protein bundle propose low selectivity.
E5蛋白是一种由高危型人乳头瘤病毒16型（HPV - 16）编码的、含有83个氨基酸的多跨膜结构膜蛋白，具有三个跨膜结构域（TMDs）。HPV - 16被发现是宫颈癌的致病因子。E5蛋白与其他蛋白（如E6、E7）一样，在细胞发生恶变的“早期”（E期）表达。实验发现，E5形成六聚体组装体，通过使脂质膜对离子和小分子具有通透性，表现出所谓的通道形成蛋白类的特征。利用基于力场的对接方法，E5蛋白被用于构建组装束中该蛋白的结构模型。在完全水合的脂质双层中对选定束进行的扩展分子动力学模拟表明，第二个TMD构成孔衬，使得水柱能够存在于孔腔内。完全相关性分析表明束单体内部存在不对称动力学。对蛋白束假定开放孔的快照结构进行平均力势计算，结果显示选择性较低。
