RepA is a protein that sticks to the beginning of the plasmid's DNA sequence and starts the copying process. "This protein is essential to everything," Schumacher said. "If you don't have it, the plasmid will quickly cease to exist."
Plasmids also need a mechanism to prevent themselves from making too many copies, which would strangle their bacterial host. The researchers have found that RepA is crucial to that function as well.
RepA naturally sticks together in pairs. When a pair of RepA proteins bumps into another pair, as when the cell is starting to get crowded with plasmids, the two pairs of RepA preferentially stick to each other. They form a complex back-to-back, with both having their DNA-grabbing parts facing outward.
When RepA forms this four-part molecule, the plasmids are said to be 'handcuffed,' because two rings of DNA are captured with the locked-up and non-functional RepA complex in the middle.
Once it is handcuffed like this, the plasmid will no longer replicate. Schumacher said this mechanism is apparently how RepA prevents the plasmids from overpopulating the bacterial cell.
Schumacher says RepA is ubiquitous in the plasmid world and doesn't bear much resemblance to other proteins, or to human proteins, making it an attractive drug target. She is hopeful the molecule could be a new site to attack with antibiotics.
"This has been a fun project because we saw many things we didn't expect to see," Schumacher said.
|Contact: Karl Leif Bates|