The initial protomer latches onto one of the four "letters" that make up the RNA code, in particular, the "U," which stands for a component of RNA called uridine. The other protomer "counts" RNA letters starting from the U, skips exactly one letter, then cuts the RNA.
Although the enzyme can slice any RNA, even that of the body's own cells, it only does so when activated by interferon.
"We were surprised to find that the two protomers were identical but have different roles, one binding and one slicing," Korennykh said. "Enzymes usually have distinct sites that bind the substrate and catalyze reactions. In the case of RNase L, it appears that the same exact protein surface can do both binding and catalysis. One RNase L subunit randomly adopts a binding role, whereas the other identical subunit has no other choice but to do catalysis."
To discover the enzyme's structure, the researchers first created a crystal of the RNase L enzyme. The main challenge was finding the right combination of chemical treatments that would force the enzyme to crystallize without destroying it.
Korennykh groupAfter much trial and error and with the help of an automated system, postdoctoral research associate Jesse Donovan and graduate student Yuchen Han succeeded in making the crystals.
Next, the crystals were bombarded with powerful X-rays, which diffract when they hit the atoms in the crystal and form patterns indicative of the crystal's structure. The diffraction patterns revealed how the atoms of RNase L are arranged in 3D space.
At the same time Sneha Rath, a graduate student in Korennykh's laboratory, worked on understanding the RNA cleavage mechanism of RNase L using synthetic RNA fragments. Rath's results matched the structural fi
|Contact: Catherine Zandonella|