Beaming of X-rays at immobilized molecules could lead to new methods to fight HIV and retrovirus-based cancers.
An experimental procedure using X-rays to immobilize molecules is making waves in the research world and could help contribute to the development of new therapies for HIV.
The procedure allowed researchers to uncover how RSV — a retrovirus that causes cancer – brings together copies of the protein retroviral integrase to integrate into the infected cells DNA, making more retroviruses.
"It can certainly help with the development of anti-retrovirals to target the integrase functions," said senior author Hideki Aihara. "Ultimately, we want to inhibit HIV integration, and for that purpose we need to know HIV integrase’s complex structure."
Over the course of several years, researchers had to find a way to successfully make a stable protein-DNA complex the correct size in order to have it immobilize in crystalline form.
The next step used X-rays to capture data on the X-ray beams as it travels through the crystal. In order to determine the precise configuration of the freeze framed molecules, researchers used the Minnesota Supercomputing Institute computing capabilities. These calculations took approximately 3 additional years.
The results of the study, published in Nature, showed that RSV uses a complex of 8 integrase molecules to position the host and viral DNA to connect. This discovery was surprising because other viruses only uses 4 integrase molecules.
"The structure looked very different from what we anticipated," Aihara said. "Initially it looked odd, but we started looking into details and it sort of all made sense."
Researchers are looking to perform the same experiment using HIV integrase, which is notably more difficult than RSV integrase. However, the results would be much more useful and beneficial for developing anti-HIV therapies.
"We would really like to see whether this unexpected assembly is also the case for HIV," Aihara said. "We think it is, but we (need) evidence."