STRUCTURAL STUDIES OF PROTEIN SUBUNITS

抗体是抵抗病毒感染的主要防线。 然而，很少有人了解抗体的机制， 中立化和承认。 在文献中有很多关于是否 抗体可以诱导病毒体衣壳中的总体构象变化。 一些研究表明，这种变化会导致病毒中和，而 另一些人则声称，汇总就足够了。 我们希望最终 确定抗体诱导构象的存在和作用 变化 众所周知，肽疫苗在诱导中和抗体方面很差 在动物身上。 一个值得注意的例外是口蹄疫病毒（FMDV） 其中大的柔性环是主要的抗原特征。 通过 研究抗原的哪些方面（例如形状和电荷） 在抗体识别中很重要， 合成疫苗 一些抗人鼻病毒14的单克隆抗体可结合双链霉菌， 病毒粒子的表面 到目前为止，还没有对 以这种方式结合的抗体。 该结构将有助于定义 抗体结构域之间的柔性程度。 为了实现上述目标，将检查抗体中和 在结构上有几个层次。 Fab 17-IA的结构将是 在图像重建的背景下进行改进和进一步检查， Fab 17-IA/HRV 14复合物。 结构研究将在 逃逸突变体和Fab 17-IA/HRV 14复合物的晶体。 将对逃逸突变体的晶体进行结构研究 和Fab 17-IA/HRV 14复合物的活性。 Fab接触的程度和 个别残留物的重要性将通过特定地点的 诱变 抗体二价连接和构象变化 将通过进一步的电子显微镜研究进行检查， 的Fab 17-IA/HRV 14复合物。

Antibodies are a major line of defense against viral infections. However, little is understood as to the mechanisms of antibody neutralization and recognition. There has been a lot of discussion in the literature as to whether antibodies can induce gross conformational changes in the virion capsid. Some studies suggest that such changes cause viral neutralization whereas others claim that aggregation is sufficient. We hope to finally determine the existence and role of antibody induced conformational changes. Peptide vaccines are notoriously bad at inducing neutralizing antibodies in animals. A notable exception is foot and mouth disease virus (FMDV) where a large flexible loop is the dominant antigenic feature. By studying what aspects (e.g. shape and charge) of the antigen are important in antibody recognition, it may be possible to improve synthetic vaccines. Some monoclonal antibodies to human rhinovirus 14 may bind bivalently to the surface of a virion. To date, there has not been the examination of an antibody bound in such a way. This structure will help define the extent of flexibility between domains of antibodies. To accomplish the above goals, antibody neutralization will be examined structurally at several levels. The structure of Fab17-IA will be refined and further examined in context of the image reconstruction of the Fab17-IA/HRV14 complex. Structural studies will be carried out on the crystals of escape mutants and of the Fab17-IA/HRV14 complex. Structural studies will be carried out on the crystals of escape mutants and of the Fab17-IA/HRV14 complex. The extent of Fab contact and importance of individual residues will be tested by site-specific mutagenesis. Antibody bivalent attachment and conformational changes will be examined by further electron microscopy studies and the structure of the Fab17-IA/HRV14 complex.