肺炎链球菌是引起人类肺炎、中耳炎和脑膜炎的主要致病菌，每年导致全球超过160万人死亡。我们前期对参与肺炎链球菌粘附和侵染的富含丝氨酸糖蛋白PsrP进行了系统的研究。但是尚不清楚PsrP是如何通过辅助型分泌系统SecA2/SecY2而定位于细胞壁外的。我们将利用X射线晶体学和冷冻电镜手段，解析该辅助型分泌系统的核心复合物SecA2-SecY2-Asp4-Asp5以及外围复合物Asp1-3的三维结构，并基于结构对其分子功能和作用机制进行深入研究，揭示Asp1-3参与底物糖基化与转运分泌的耦联机制，并最终阐明SecY2/SecA2分泌系统转运和分泌PsrP的分子机制。本研究将为研发防治肺炎链球菌的药物和疫苗提供结构基础。

The human pathogen Streptococcus pneumoniae is responsible for many infectious diseases, such as pneumonia, otitis media and meningitis, leading to over 1.6 million deaths annually in the world. We have systematically investigated the serine-rich repeat glycoprotein PsrP, which is related to the adhesion and invasion of S. pneumoniae. However, how this glycoprotein is secreted and localized at the cell surface via the accessory secretion system SecY2/SecA2 remains unknown. Here we will apply the crystallography and cryo-electron microscopy to solve the 3-D structures of the core complex SecA2-SecY2-Asp4-Asp5, and the accessory complex Asp1-3. Based on these structures, we will explore the molecular function and working mechanism of this system. These findings will illustrate the mechanisms how PsrP precursor is glycosylated and transported coupled by Asp1-3, and eventually secreted via SecY2/SecA2 system. The results will provide hints for rational design of inhibitors/vaccines against pneumococci related diseases.