Important new information on one of the most critical protein machines in living cells has been reported by a team of researchers with the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley. The researchers have provided the most detailed look ever at the "regulatory particle" used by the protein machines known as proteasomes to identify and degrade proteins that have been marked for destruction. The activities controlled by this regulatory particle are critical to the quality control of cellular proteins, as well as a broad range of vital biochemical processes, including transcription, DNA repair and the immune defense system.
"Using electron microscopy and a revolutionary new system for protein expression, we have determined at a subnanometer scale the complete architecture, including the relative positions of all its protein components, of the proteasome regulatory particle," says biophysicist Eva Nogales, the research team's co-principal investigator. "This provides a structural basis for the ability of the proteasome to recognize and degrade unwanted proteins and thereby regulate the amount of any one type of protein that is present in the cell."
Says the team's other co-principal investigator and corresponding author, biochemist Andreas Martin, "While the biochemical function of many of the proteasome components have been determined, and some subnanometer structures have been identified, it was unclear before now which component goes where and which components interact with one another. Now we have a much better understanding as to how the proteasome machinery works to control cellular processes and this opens the possibility of manipulating proteasome activity for the treatment of cancer and other diseases."
Nogales, who holds appointments with Berkeley Lab, UC Berkeley, and the Howard Hughes Medical Institute, and Martin, who holds appointments with
|Contact: Lynn Yarris|
DOE/Lawrence Berkeley National Laboratory