As HIV appears to outmaneuver even the latest drug combinations, researchers are scrambling for new attack strategies. New molecular details about one HIV protein may provide just that--the basis for an entirely new class of highly specific anti-AIDS drugs.
Scientists working with support from NIH's National Institute of General Medical Sciences have determined the three-dimensional molecular structure of the HIV nucleocapsid protein bound to the virus' genetic material (RNA, or ribonucleic acid). The nucleocapsid protein is responsible for stuffing viral genes into new viral particles. The protein is a prime target for anti-AIDS drugs, because previous studies have shown that when it is crippled, HIV cannot spread to other cells. New drugs that block the action of the RNA component could be equally important.
The detailed structure of the protein-RNA complex, determined using a technique called nuclear magnetic resonance (NMR) spectroscopy, is published in the January 16 issue of Science.
"The structure is significant for two main reasons. First, it provides molecular insights into how the protein recognizes and binds to [a specific site on viral] RNA. Second, it provides a structural basis for the development of drugs that are designed to disrupt this recognition and binding, and thus prevent the spread of the virus," said Dr. Michael F. Summers, lead author of the study and a professor of biophysical and bioinorganic chemistry at the University of Maryland Baltimore County (UMBC). Dr. Summers is also an associate investigator of the Howard Hughes Medical Institute.
Like a father recognizing his child in a crowded classroom, nucleocapsid plucks
from the infected cellular melange only the specific viral RNA needed to form
new viral particles. Nucleocapsid recognizes and binds to only the few RNA
strands that contain a site called the packaging domain, said coauthor Dr.
Contact: Alisa Zapp Machalek
NIH/National Institute of General Medical Sciences