Buts Lieven, Lah Jurij, Dao-Thi Minh-Hoa, Wyns Lode, Loris Remy
Laboratorium voor Ultrastructuur, Vrije Universiteit Brussel, and Department of Molecular and Cellular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie, Pleinlaan 2, B-1050 Brussel, Belgium.
Trends Biochem Sci. 2005 Dec;30(12):672-9. doi: 10.1016/j.tibs.2005.10.004. Epub 2005 Oct 28.
Bacterial genomes frequently contain operons that encode a toxin and its antidote. These 'toxin-antitoxin (TA) modules' have an important role in bacterial stress physiology and might form the basis of multidrug resistance. The toxins in TA modules act as gyrase poisons or stall the ribosome by mediating the cleavage of mRNA. The antidotes contain an N-terminal DNA-binding region of variable fold and a C-terminal toxin-inhibiting domain. When bound to toxin, the C-terminal domain adopts an extended conformation. In the absence of toxin, by contrast, this domain (and sometimes the whole antidote protein) remains unstructured, allowing its fast degradation by proteolysis. Under silent conditions the antidote inhibits the toxin and the toxin-antidote complex acts as a repressor for the TA operon, whereas under conditions of activation proteolytic degradation of the antidote outpaces its synthesis.
细菌基因组通常包含编码毒素及其解毒剂的操纵子。这些“毒素-抗毒素（TA）模块”在细菌应激生理学中发挥重要作用，可能构成多药耐药性的基础。TA模块中的毒素充当回旋酶毒物或通过介导mRNA的切割使核糖体停滞。解毒剂包含可变折叠的N端DNA结合区域和C端毒素抑制结构域。当与毒素结合时，C端结构域呈伸展构象。相比之下，在没有毒素的情况下，该结构域（有时是整个解毒剂蛋白）仍无结构，使其能够通过蛋白水解快速降解。在沉默条件下，解毒剂抑制毒素，毒素-解毒剂复合物充当TA操纵子的阻遏物，而在激活条件下，解毒剂的蛋白水解降解速度超过其合成速度。
