WIKIMEDIA, ROGERDODDCells dispose of worn-out proteins to maintain normal function. One type of protein degradation relies upon such proteins being tagged with peptides called ubiquitins so that the cell can recognize them as trash. Harvard researcher Marc Kirschner and his colleagues have used single-molecule fluorescence methods to show how an enzyme adds ubiquitins to proteins, and how those proteins are recognized and recycled in the cell’s proteosome. They reported their findings in a pair of Science papers published last week (April 10).
Aaron Ciechanover, Avram Hershko, and Irwin Rose, the researchers who discovered the process in the 1980s, shared the 2004 Nobel Prize in Chemistry for their work on ubiquitin-mediated protein degradation. But the molecular particulars of the process remained murky until last week. Kirschner and his colleagues found that an enzyme called APC/C adds ubiquitins to proteins headed for the rubbish heap in an iterative fashion, through processive affinity amplification. They also found that the proteosome singles out ubiquitin-tagged proteins for degradation by recognizing distributed arrays of short ubiquitins chains, with the configuration of those chains determining how the protein passes through specific channels in the proteosome. Previous models posited that proteins tagged with tetraubiquitins were the only ones slated for degradation.
“Both studies substantially enrich our knowledge of ubiquitination and degradation, reveal new properties of APC/C and the proteasome, and challenge established concepts about the ubiquitin-proteasome system,” wrote David Komander, a researcher at the Medical Research Council Laboratory of Molecular Biology in the U.K. in a commentary in Science.