CRYSTALLOGRAPHY OF HUMAN PAPILLOMAVIRUS E2

乳头瘤病毒E2蛋白是病毒生命的关键调节因子 循环，控制几个重要功能。 它刺激 通过协同结合病毒复制起点进行复制 病毒解旋酶E1 它激活了许多 病毒启动子，调节癌蛋白E6和E7的水平， 他人 最后，它似乎参与了病毒 基因组与宿主细胞染色体的结合，以确保忠实分离 在有丝分裂期间。 对这些功能中的每一个都至关重要的残基 已被定位到约200个氨基酸的N-末端激活结构域 acids. 显然，这个区域的结构充满了 对蛋白质功能的潜在见解，特别是因为 还没有分离的真核生物激活结构域结构 解决了 去年根据这项建议开展的工作使我们能够解决一个 144个氨基酸片段的激活结构域，导致新的想法， 蛋白质的关键特征和相应的诱变研究。 我们 也有一个结构的晶体， 域，并希望扩大我们对这种变体的研究。 的 晶体具有长针/棒形态， 强X射线源，如同步加速器。 我们已经证明， 将在同步加速器上以相对较长的时间加速到至少2.3 E 曝光时间 我们的目标是解决这个结构更长 构建体

The papillomavirus E2 protein is a key regulator of viral life cycle, controlling several important functions. It stimulates replication by cooperatively binding the viral origin of replication with the viral helicase E1. It activates transcription from many viral promoters, regulating levels of the oncoproteins E6 and E7 among others. Finally, it appears to be involved in tethering the viral genome to the host cell chromosomes to ensure faithful segregation during mitosis. Residues crucial for each of these functions have been mapped to the N-terminal activation domain of about 200 amino acids. Evidently then, the structure of this region is full of potential insights into the protein's function, particularly since there have been no isolated eukaryote activation domain structures solved. Last year's work under this proposal allowed us to solve a 144 amino acid piece of the activation domain, leading to new ideas on the protein's key features and corresponding mutagenesis studies. We also have crystals of a construct encompassing the full activation domain and would like to extend our studies on this variant. The crystals are of a long needle/rod morphology that benefits from a strong X-ray source such as a synchrotron. We have shown that these will diffract to at least 2.3 E on a synchrotron with relatively long exposure times. We aim to solve the structure of this longer construct.