VirB8: a conserved type IV secretion system assembly factor and drug target
VirB8: a conserved type IV secretion system assembly factor and drug target
复制标题
DOI：
10.1139/o06-148
复制
发表时间：
2006-12-01
影响因子：
2.9
通讯作者：
Baron, Christian
中科院分区：
文献类型：
--
作者：
Baron, Christian
IV型分泌系统被许多革兰氏阴性细菌用于跨细胞被膜转运大分子（蛋白质、DNA或DNA-蛋白质复合物）。其中有许多病原体的IV型分泌系统是必不可少的毒力因子。IV型分泌系统包含8-12种保守蛋白，其组装成跨越内膜和外膜的复合物，并且许多组装细胞外附件，如皮利，其起始与宿主和受体细胞的接触，随后底物易位。VirB 8是所有IV型分泌系统的必需组装因子。生物化学，细胞生物学，遗传学和酵母双杂交分析表明，VirB 8与其他IV型分泌系统的组件进行了多次相互作用，它指导极性组装的跨膜复合物在模式生物根癌农杆菌。VirB 8 X射线结构的可用性使得能够进行详细的结构-功能分析，该分析确定了VirB 4和VirB 10的结合位点以及自我相互作用位点。由于其多重相互作用，VirB 8是分析多蛋白复合物组装因子的极好模型，此外，VirB 8是靶向其蛋白质-蛋白质相互作用的药物的可能靶标，这将通过剥夺细菌的基本毒力功能来解除细菌的武装。
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.