Washington: The mystery behind an essential weapon in the body’s fight against infection has now been unlocked – a discovery that can enable new strategies for fighting infectious agents and possibly prostate cancer and obesity.
Researchers at Princeton University in New Jersey have created 3D structure of an enzyme that cuts to ribbons the genetic material of viruses and helps defend against bacteria.
“Known as RNase L, the human form of this enzyme which is a first responder in the body’s innate immune system was not understood properly till date,” said Alexei Korennykh, an assistant professor of molecular biology at Princeton University.
“Now that we have the human RNase L structure, we can begin to understand the effects of carcinogenic mutations in the RNase L gene,” he added.
For example, families with hereditary prostate cancers often carry genetic mutations in the region, or locus, encoding RNase L.
The connection is so strong that the RNase L locus also goes by the name ‘hereditary prostate cancer 1’.
The newly found structure reveals the positions of these mutations and explains why some of these mutations could be detrimental, perhaps leading to cancer, Korennykh said.
RNase L is also essential for insulin function and has been implicated in obesity.
The enzyme is an important player in the innate immune system, a rapid and broad response to invaders that includes the production of a molecule called interferon, said a paper published in the journal Science.
Interferon relays distress signals from infected cells to neighbouring healthy cells, thereby activating RNase L to turn on its ability to slice through RNA, a type of genetic material that is similar to DNA.
The result is new cells armed for destruction of the foreign RNA.
Although the enzyme can slice any RNA, even that of the body’s own cells, it only does so when activated by interferon.
“Now that the human structure has been solved, researchers can explore ways to either enhance or dampen RNase L activity for medical and therapeutic uses,” explained Korennykh.
“This work illustrates the wonderful usefulness of doing both crystallography and careful kinetic and enzymatic studies at the same time,” added Peter Walter, professor of biochemistry and biophysics at the University of California-San Francisco’s school of medicine.