Ribosome clearance by FusB-type proteins mediates resistance to the antibiotic fusidic acid
Ribosome clearance by FusB-type proteins mediates resistance to the antibiotic fusidic acid
复制标题
DOI：
10.1073/pnas.1117275109
复制
发表时间：
2012-02-07
影响因子：
11.1
通讯作者：
O'Neill, Alexander J.
中科院分区：
文献类型：
--
作者：
Cox, Georgina;Thompson, Gary S.;O'Neill, Alexander J.
人类病原体金黄色葡萄球菌对抗生素夫西地酸（FA）的耐药性通常是由FusB型蛋白（FusB或FusC）的表达引起的。这些蛋白质结合延伸因子G（EF-G），目标的FA，和救援翻译从FA介导的抑制通过一个未知的机制。在这里，我们表明，FusB家族是两个结构域的金属蛋白，其C-末端结构域包含一个四个半胱氨酸锌指与一个独特的结构折叠。该结构域介导与EF-G的C-末端结构域的高亲和力相互作用。通过与核糖体上的EF-G结合，FusB型蛋白促进在FA存在下形成的停滞的核糖体.EF-G.GDP复合物的解离，从而允许核糖体恢复翻译。这些蛋白质的核糖体清除代表了一种非常不寻常的抗生素耐药机制，这似乎是由FusB型蛋白质，核糖体和EF-G的相对丰度微调。
Resistance to the antibiotic fusidic acid (FA) in the human pathogen Staphylococcus aureus usually results from expression of FusB-type proteins (FusB or FusC). These proteins bind to elongation factor G (EF-G), the target of FA, and rescue translation from FA-mediated inhibition by an unknown mechanism. Here we show that the FusB family are two-domain metalloproteins, the C-terminal domain of which contains a four-cysteine zinc finger with a unique structural fold. This domain mediates a high-affinity interaction with the C-terminal domains of EF-G. By binding to EF-G on the ribosome, FusB-type proteins promote the dissociation of stalled ribosome.EF-G.GDP complexes that form in the presence of FA, thereby allowing the ribosomes to resume translation. Ribosome clearance by these proteins represents a highly unusual antibiotic resistance mechanism, which appears to be fine-tuned by the relative abundance of FusB-type protein, ribosomes, and EF-G.