STRUCTURE/ACTIVITY OF A MEMBER OF THE VAPBC FAMILY OF TOXIN ANTITOXIN SYSTEMS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在原核生物中，同源毒素-抗毒素对早已为人所知，但结核分枝杆菌的任何给定复合体都没有可用的3D结构。在这里，我们报道了结核分枝杆菌VapBC复合体家族中的一个成员的晶体结构和活性。VapC-5毒素是一种紧凑的，150个残基，两个结构域的蛋白。在毒素周围弯曲的是VAPB-5抗毒素，它是一个33个残基的阿尔法螺旋。分析表明，该毒素是一种镁激活的内切核酸酶，被抗毒素抑制。DNase活性的缺乏与早期的观点一致，即该复合体抑制了自己的操纵子。此外，对抗毒素与毒素结合的相互作用的分析表明，需要精细的控制来保护细菌细胞免受有毒的VapC-5的伤害。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In prokaryotes, cognate toxin-antitoxin pairs have long been known, but no 3D structure has been available for any given complex from Mycobacterium tuberculosis. Here we report the crystal structure and activity of a member of the VapBC family of complexes from M. tuberculosis. The toxin VapC-5 is a compact, 150 residues, two domain ¿/¿ protein. Bent around the toxin is the VapB-5 antitoxin, a 33 residue alpha helix. Assays suggest that the toxin is an Mg-enabled endoribonuclease, inhibited by the antitoxin. The lack of DNase activity is consistent with earlier suggestions that the complex represses its own operon. Furthermore, analysis of the interactions in the binding of the antitoxin to the toxin suggest that exquisite control is required to protect the bacteria cell from toxic VapC-5.