Molecular Characterization of host-specific and –unspecific properties of IdeC, the IgG-specific protease of Streptococcus canis

与犬链球菌（S.）类似，一种通常与狗和猫有关的兼性病原体，50多种不同的链球菌中有许多表现出显著的宿主特异性。迄今为止，对宿主特异性背后的分子基础知之甚少，尽管IdeS/Mac家族的免疫球蛋白（Ig）特异性蛋白酶似乎起着重要作用。该项目将集中研究犬链球菌的igg特异性蛋白酶IdeC。利用分子生物学和蛋白质生物化学方法，我们将确定IdeC对犬和猫IgG的宿主特异性机制，并通过合理的蛋白质设计，确定如何改变和/或扩展宿主特异性。此外，许多IdeS/Mac家族蛋白酶在蛋白质序列中含有RGD基序。由于RGD基序涉及宿主细胞整合素的一般、非物种识别，我们还将使用分子和细胞生物学方法确定IdeC作为粘附素或入侵宿主细胞的作用。

Similar to Streptococcus (S.) canis, a facultative pathogen generally found associated with dogs and cats, many of the more than 50 different Streptococcus species show remarkable host specificities. To date, little is known about the molecular bases behind the host-specificities, although immunoglobulin (Ig)-specific proteases of the IdeS/Mac family appear to play an important role. This project will concentrate on IdeC, the IgG-specific protease of S. canis. Using molecular biological and protein biochemistry methods, we will determine the mechanism of the host-specificity of IdeC for canine and feline IgG, and using rational protein design, determine how the host-specificity can be altered and/or extended. In addition, many of the IdeS/Mac family proteases harbor an RGD motif in the protein sequence. As RGD motifs are implicated in general, species-independent recognition of host cell integrins, we will also determine the role for IdeC as an adhesin or invasin of host cells using molecular and cell biology methods.