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17 April 2014 12:48 pm ,
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Officials last week revealed that the U.S. contribution to ITER could cost $3.9 billion by 2034—roughly four times the...
An experimental hepatitis B drug that looked safe in animal trials tragically killed five of 15 patients in 1993. Now,...
Using the two high-quality genomes that exist for Neandertals and Denisovans, researchers find clues to gene activity...
A new report from the Intergovernmental Panel on Climate Change (IPCC) concludes that humanity has done little to slow...
Astronomers have discovered an Earth-sized planet in the habitable zone of a red dwarf—a star cooler than the sun—500...
Three years ago, Jennifer Francis of Rutgers University proposed that a warming Arctic was altering the behavior of the...
- 17 April 2014 12:48 pm , Vol. 344 , #6181
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A Molecular Inspector
5 December 1997 8:00 pm
Like any production line, a cell's protein-forming machinery occasionally makes mistakes. When it does, molecules called ubiquitins mark the duds for destruction. A paper in today's Science describes a protein that not only holds this tagging machinery together, but helps confiscate misfolded proteins before they can be mistakenly exported from the cell.
Proteins destined for export, such as a hormone, are stuffed into internal tubules called the endoplasmic reticulum (ER) as they are being made. Once inside, the proteins fold into their proper shape and are shuttled to the cell membrane for release. But if they misfold, the proteins are ejected from the ER back into the cell cytoplasm, where they are tagged and then destroyed by agglomerations of other proteins. Two proteins, Ubc6p and Ubc7p, are known to help tag secreted proteins in yeast, but Thomas Sommer, a molecular biologist at the Max Delbrück Center for Molecular Medicine in Berlin, thought they weren't acting alone. He wanted to find additional proteins involved in the process--particularly those that might help remove misfolded proteins from the ER.
To identify other proteins involved in the ubiquitin-tagging pathway, Sommer and his colleagues prepared special filters with ubiquitin. They added proteins that had been bound to the ER membrane, reasoning that only proteins involved in tagging would bind to the ubiquitin-tagging machinery in the filter. When they added a chemical to break any of the resulting bonds, one protein was released, which they named Cue1p. Further experiments revealed that Cue1p binds to the tagging protein Ubc7p.
To find out where Cue1p acts, Sommer and his colleagues used a yeast strain that makes a deformed protein. In yeast that lack the gene for either Cue1p or Ubc7p, the misfolded protein remained in the ER and was never tagged with ubiquitin. Sommer and his colleagues think that Ubc7p in the cell's cytoplasm binds to Cue1p, forming a complex that both escorts misfolded proteins out of the ER and tags them for destruction.
By tagging the protein right away, the complex may be preventing misfolded proteins from reentering the ER, says Howard Riesman, a molecular biologist at the Biozentrum of the University of Basel in Switzerland. The same complex may apply not just to secreted proteins, but also to ones intended for internal use by the cell, which are folded in the cytoplasm.