Meydan Sezen, Klepacki Dorota, Karthikeyan Subbulakshmi, Margus Tõnu, Thomas Paul, Jones John E, Khan Yousuf, Briggs Joseph, Dinman Jonathan D, Vázquez-Laslop Nora, Mankin Alexander S
Center for Biomolecular Sciences-m/c 870, University of Illinois at Chicago, 900 S. Ashland Avenue, Chicago, IL 60607, USA.
Proteomics Center of Excellence, Northwestern University, 633 Clark Street, Chicago, IL 60208, USA.
Mol Cell. 2017 Jan 19;65(2):207-219. doi: 10.1016/j.molcel.2016.12.008.
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 aa-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.
金属离子外排泵维持细胞内的离子稳态。这些转运蛋白的功能通常由伴侣蛋白支持，伴侣蛋白从细胞质中清除金属离子。虽然大肠杆菌中的铜离子转运蛋白CopA已为人所知，但其伴侣蛋白的基因尚未被鉴定。我们发现CopA伴侣蛋白在大肠杆菌中由编码该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读框终止翻译，并产生70个氨基酸长的多肽CopA(Z)，它帮助细胞在有毒的铜浓度下存活。移码的高效率是由一个“滑溜”序列、一个mRNA假结和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基因中发现，也存在于copA的人类同源物ATP7B中，并在体内指导核糖体移码。
