"This step-by-step process requires that all the molecules be brought together in a specific manner so the reactions can take place quickly," Schulman said. "That's where the E2 tail comes into play. The shape and location of E2's tail make it perfectly suited for drawing E1 close to NEDD8 so those two proteins can rapidly bind to each other and begin the process of assembling the on switch." The workshop's ability to quickly assemble the on switch is important because it reflects the need for cells to be able to react swiftly to a changing environment, according to Martine Roussel, Ph.D., member of St. Jude Genetics and Tumor Cell Biology and an author of the paper.
"Cells must be able to respond quickly to the changing demands and cues of their internal and external environments," Roussel said. "Often, the best way to respond rapidly is for the cell to modify a particular protein that already exists, rather than take the time to make a new one. Once modified, the existing protein becomes active and can quickly set off a specific cascade of biochemical reactions that performs a specific function in the cell."
The E1, E2 and E3 enzymes that make up the workshop that prepares NEDD8 to modify Cul1 are variations of a larger family of similar enzymes, according to the researchers. These other enzymes are part of the so-called ubiquitin pathway that puts molecular tags on proteins to signal that they should be destroyed. The ubiquitin pathway has dozens of different types of E2 enzymes, hundreds of different types of E3 enzymes and thousands of different targets. The NEDD8 workshop, however, has only one E2 and a few E3 enzymes, and NEDD8 itself has only a few target molecule
Contact: Bonnie Cameron
St. Jude Children's Research Hospital