Baron Christian
McMaster University, Department of Biology and Antimicrobial Research Centre, 1280 Main St. West, Hamilton, ON LS8 4K1, Canada.
Biochem Cell Biol. 2006 Dec;84(6):890-9. doi: 10.1139/o06-148.
Type IV secretion systems are used by many gram-negative bacteria for the translocation of macromolecules (proteins, DNA, or DNA-protein complexes) across the cell envelope. Among them are many pathogens for which type IV secretion systems are essential virulence factors. Type IV secretion systems comprise 8-12 conserved proteins, which assemble into a complex spanning the inner and the outer membrane, and many assemble extracellular appendages, such as pili, which initiate contact with host and recipient cells followed by substrate translocation. VirB8 is an essential assembly factor for all type IV secretion systems. Biochemical, cell biological, genetic, and yeast two-hybrid analyses showed that VirB8 undergoes multiple interactions with other type IV secretion system components and that it directs polar assembly of the membrane-spanning complex in the model organism Agrobacterium tumefaciens. The availability of the VirB8 X-ray structure has enabled a detailed structure-function analysis, which identified sites for the binding of VirB4 and VirB10 and for self-interaction. Due to its multiple interactions, VirB8 is an excellent model for the analysis of assembly factors of multiprotein complexes. In addition, VirB8 is a possible target for drugs that target its protein-protein interactions, which would disarm bacteria by depriving them of their essential virulence functions.
许多革兰氏阴性菌利用IV型分泌系统将大分子（蛋白质、DNA或DNA-蛋白质复合物）转运穿过细胞壁。其中有许多病原体，IV型分泌系统是它们必不可少的毒力因子。IV型分泌系统由8至12种保守蛋白组成，这些蛋白组装成一个跨越内膜和外膜的复合物，许多还组装细胞外附属物，如菌毛，菌毛启动与宿主细胞和受体细胞的接触，随后进行底物转运。VirB8是所有IV型分泌系统必不可少的组装因子。生化、细胞生物学、遗传学和酵母双杂交分析表明，VirB8与其他IV型分泌系统成分发生多种相互作用，并且它指导模式生物根癌农杆菌中跨膜复合物的极性组装。VirB8的X射线结构的可得性使得能够进行详细的结构-功能分析，该分析确定了VirB4和VirB10的结合位点以及自相互作用位点。由于其多种相互作用，VirB8是分析多蛋白复合物组装因子的极佳模型。此外，VirB8是针对其蛋白质-蛋白质相互作用的药物的可能靶点，这些药物通过剥夺细菌必需的毒力功能来使细菌失去活性。
