STRUCTURAL STUDIES OF PROTEIN SUBUNITS

这项建议的目的是继续审查 抗体介导的中和 小核糖核酸病毒，并启动复制的结构研究 复杂. 结合分子生物学， 晶体学和低温电子显微镜，我们正在研究 几种不同抗体单独和复合的结构 人类鼻病毒14 通过这些研究，我们希望 阐明抗体中和的结构机制， 确定为什么抗体中和的结构原因 不同的功效，并解决（和澄清）目前的一些 关于中立化的教条。 此外，这些研究有助于 我们更好地了解抗体结构/功能的其他方面 灵活性和体细胞超突变等关系。 通过 更好地理解需要哪些化学相互作用 识别，并通过识别参与的关键结构过程， 中和，我们希望这项工作将有助于发展 针对其他病毒病原体的疫苗。 我们也已经开始工作 关于非结构蛋白的结构/功能，3A。 这 这种蛋白质通过一种未知的 机制，似乎是一个新的抗病毒药物的目标， 环草素 因此，所有这些拟议的工作都在研究如何 人们可以通过天然或药物来控制病毒感染 剂.

The objective of this proposal is to continue our examination of the mechanism of antibody-mediated neutralization of picornaviruses and to initiate structural studies on the replication complex. Using a combination of molecular biology, crystallography, and cryo-electron microscopy, we are examining the structures of several different antibodies alone and complexed with human rhinovirus 14. Through these studies, we hope to elucidate the structural mechanism of antibody-neutralization, to ascertain the structural reasons for why antibodies neutralize with varied efficacies, and to address (and clarify) some of the current dogmas concerning neutralization. In addition, these studies help us to better understand other aspects of antibody structure/function relationships such as flexibility and somatic hypermutations. By better understanding what chemical interactions are required for recognition, and by identify the key structural processes involved in neutralization, we hope this work will aid the development of vaccines against other viral pathogens. We have also started work on the structure/function of the non-structural protein, 3A. This protein activates the viral RNA polymerase via an yet unknown mechanism and seems to be a target for a new anti-viral agent, enviroxine. Therefore, all of this proposed work is examining how one can control viral infections either by natural or pharmaceutical agents.