Efb是金黄色葡萄球菌分泌的一种重要的毒力因子，与细菌致病和免疫逃逸密切相关。前期研究发现，Efb对巨噬细胞NF-κB信号通路的激活有明显的抑制作用，但其机制并不清楚。进一步研究发现Efb与NF-κB信号通路关键蛋白TRAF3之间存在直接的相互作用，而TRAF3本身可通过泛素化降解发挥对NF-κB信号通路的负调控作用。据此我们推测金黄色葡萄球菌通过分泌Efb蛋白与TRAF3相互作用，掩盖了后者的泛素化位点或改变了其空间构象，从而阻断TRAF3的泛素化降解，发挥对NF-κB信号通路的抑制作用。基于此，本研究拟在前期研究基础上进一步鉴定Efb和TRAF3相互作用的关键结构域，解析Efb、TRAF3及其复合物的晶体结构，明确参与作用的关键残基及复合物的形成对TRAF3空间构象的影响。同时，通过细胞、动物实验探讨Efb抑制NF-κB信号通路激活的具体机制及结构基础，阐明Efb在细菌致病中的作用。

Efb is an important virulence factor secreted by Staphylococcus aureus (S. aureus) and it is participated in the pathogenesis and immune escape of the bacteria. Previous studies have found that Efb has a significant inhibitory effect on macrophage NF-κB signaling pathway activation, but the mechanism remains unclear. Further studies revealed that there is a direct interaction between Efb and TRAF3, a key molecule involved in NF-κB signaling pathway, and TRAF3 itself can inhibit NF-κB signaling pathway through ubiquitination mediated degradation. Thus, we hypothesized that the interaction between Efb and TRAF3 may block the ubiquitination site or changes the spatial conformation of TRAF3, thus blocking the ubiquitination mediated degradation of TRAF3 and maintaining its inhibition of NF-κB signaling pathway. This study aims to explore the specific mechanism of the inhibitory effect of Efb on NF-κB signaling. Firstly, we will identify the key domains that involved in the interaction between Efb and TRAF3. Secondly, we will determine the structure of Efb-TRAF3 complex, and identify the key residues involved in the interaction. Finally, we will explored the specific mechanism of Efb inhibition on NF-κB signaling pathway by in vivo and in vitro studies, and further elucidate the role of Efb in bacterial pathogenesis.