Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene.
Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene.
复制标题
编程的核糖体框架从同一基因产生铜转运蛋白和铜伴侣。
DOI：
10.1016/j.molcel.2016.12.008
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发表时间：
2017-01-19
期刊：
影响因子：
16
通讯作者：
Mankin AS
中科院分区：
文献类型：
--
作者：
Meydan S;Klepacki D;Karthikeyan S;Margus T;Thomas P;Jones JE;Khan Y;Briggs J;Dinman JD;Vázquez-Laslop N;Mankin AS
金属外排泵维持细胞内的离子稳态。转运蛋白的功能通常由伴侣蛋白辅助，伴侣蛋白从细胞质中清除金属离子。尽管大肠杆菌中已知铜离子转运蛋白CopA，但尚未鉴定出其伴侣蛋白的基因。我们表明，CopA伴侣蛋白在大肠杆菌中由编码转运蛋白的同一基因表达。一些翻译copA的核糖体发生程序性移码，在 -1读码框终止翻译，并产生70个氨基酸长的多肽CopA（Z），它有助于细胞在有毒的铜浓度下存活。移码的高效率是通过一个“滑动”序列、一个mRNA假结以及CopA新生链的联合刺激作用实现的。类似的mRNA元件不仅在其他细菌的copA基因中被发现，也存在于copA的人类同源基因ATP7B中，并在体内指导核糖体移码。
Metal efflux pumps maintain ion homeostasis in the cell. The functions of the transporters are often supported by chaperone proteins, which scavenge the metal ions from the cytoplasm. Although the copper ion transporter CopA has been known in Escherichia coli, no gene for its chaperone had been identified. We show that the CopA chaperone is expressed in E. coli from the same gene that encodes the transporter. Some ribosomes translating copA undergo programmed frameshifting, terminate translation in the -1 frame, and generate the 70 amino acid-long polypeptide CopA(Z), which helps cells survive toxic copper concentrations. The high efficiency of frameshifting is achieved by the combined stimulatory action of a ‘slippery’ sequence, an mRNA pseudoknot, and the CopA nascent chain. Similar mRNA elements are not only found in the copA genes of other bacteria but are also present in ATP7B, the human homolog of copA, and direct ribosomal frameshifting in vivo.