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5 December 2013 11:26 am ,
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Researchers have been hot on the trail of the elusive Denisovans, a type of ancient human known only by their DNA and...
Thousands of scientists in the Russian Academy of Sciences (RAS) are about to lose their jobs as a result of the...
Dyslexia, a learning disability that hinders reading, hasn't been associated with deficits in vision, hearing, or...
Exotic, elusive, and dangerous, snakes have fascinated humankind for millennia. They can be hard to find, yet their...
Researchers have sequenced and analyzed the first two snake genomes, which represent two evolutionary extremes. The...
Snake venoms are remarkably complex mixtures that can stun or kill prey within minutes. But more and more researchers...
At age 30, Dutch biologist Freek Vonk has built up a respectable career as a snake scientist. But in his home country,...
Since arriving on the island of Guam in the 1940s, the brown tree snake ( Boiga irregularis ) has extirpated native...
- 5 December 2013 11:26 am , Vol. 342 , #6163
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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.