STRUCTURAL STUDIES OF PROTEIN SUBUNITS

抗体是抵御病毒感染的主要防线。 然而，人们对抗体的作用机制知之甚少。 中和和认可。 在文献中有很多关于是否 抗体可以诱导病毒衣壳的大体构象变化。 一些研究表明，这种变化会导致病毒中和，而 其他人则声称，聚合就足够了。我们希望最终能 确定抗体诱导构象的存在和作用 改变。 多肽疫苗在诱导中和抗体方面是出了名的差。 在动物身上。一个值得注意的例外是口蹄疫病毒(FMDV) 其中一个大的柔性环是主要的抗原性特征。通过 研究抗原的哪些方面(如形状和电荷) 在抗体识别中的重要作用，可能会改进 合成疫苗。 某些抗人鼻病毒14的单抗可与人鼻病毒14结合 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。此结构将有助于定义 抗体区域之间的灵活性程度。 为了实现上述目标，将检查抗体中和 从结构上讲，有几个层次。Fab17-IA的结构将是 在图像重建方面进行了改进和进一步研究 Fab17-IA/HRV14复合体。将进行结构研究 逃逸突变体和Fab17-IA/HRV14复合体的晶体。 将对逃逸突变体的晶体进行结构研究 以及Fab17-IA/HRV14复合体。FAB接触的范围和 个别残留物的重要性将通过特定地点进行测试 诱变。抗体二价结合与构象变化 将通过进一步的电子显微镜研究和结构进行检查 Fab17-IA/HRV14复合体。

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.