STRUCTURAL STUDIES OF PROTEIN SUBUNITS

这项建议的目的是继续我们对 抗体介导的中和作用机制 小核糖核酸病毒和启动复制的结构研究 很复杂。结合分子生物学， 结晶学和低温电子显微镜，我们正在检查 几种不同抗体单独和复合的结构 人类鼻病毒14。我们希望通过这些研究 阐明抗体中和的结构机制，以 确定抗体与抗体中和的结构性原因 不同的有效性，并解决(和澄清)当前的一些 关于中和的教条。此外，这些研究还有助于 美国将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 更好地了解哪些化学作用是必需的 认识到这一点，并通过确定 中和，我们希望这项工作将有助于 针对其他病毒病原体的疫苗。我们也已经开始工作了 非结构蛋白3A的结构与功能这 蛋白质通过一种未知的方式激活病毒RNA聚合酶 机制，似乎是一种新的抗病毒药物的目标， 环境抗菌素。因此，所有这些拟议的工作都是在研究如何 人们可以通过自然或药物来控制病毒感染 探员们。

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.