doi:10.1038/nindia.2010.135 Published online 29 September 2010
New research has shed light on how a peptide, part of a protein, binds to a hairpin-like structure in human immunodeficiency virus (HIV-1). This binding helps the virus replicate and survive in host cells. Insights into this interaction may help design drugs against HIV.
In recent years, researchers have focused on tat, a key HIV gene which codes for a protein called Tat, rich in ariginine amino acids. The ariginine-rich peptide region of Tat protein binds to HIV-1 TAR (transactivation response) RNA. There is a lot of data available on such RNA-peptide complexes. However, there is no information on the nature of molecular forces that drive such complex formations.
The researchers undertook a thermodynamic characterization of the viral RNA-peptide interaction using a combination of spectroscopic and calorimetric techniques.
They tagged the RNA with a fluorescing agent and added peptide to the RNA solution in the presence of ultraviolet light. Fluorescence intensity rose with increasing peptide concentration. Studies showed that Tat peptide binds to two different sites of HIV-1 TAR RNA with different affinities.
The researchers mimicked the real physiological conditions of Tat peptide binding to the RNA by carrying out a salt-dependent study. It showed that only one out of five arginine residues of the peptide is involved in ionic interaction with viral RNA indicating that specificity of the interaction originates from non-polyelectrolyte contribution.
This detailed picture of the RNA-peptide binding could help design drugs that disrupt this interaction by competitive binding to either component, lead researcher Souvik Maiti says.