A team of researchers from University of Illinois has solved the mystery of how a protein associated with the HIV virus can cross cell membranes. Their findings could improve the design of therapeutic agents that cross a variety of such membranes.
The TAT protein transduction domain of the HIV virus is a tiny part of the overall TAT protein (containing only 11 amino acids), but it can slip across lipid-rich membranes that are designed to keep things out. Although it is not involved in transmitting HIV, TAT aids the passage of other materials across the membranes of infected cells.
Research has pointed to one of its amino acids called arginine, as the one responsible for the activity. They explained that most membranes are composed of a double layer of neutral, water-repellent lipids on their interiors with hydrophilic (water-loving) "head groups" on their internal and external surfaces.
The head groups generally carry a mildly negative charge, and can attract positively-charged arginine. This results to the deformation of the membrane, making it porous (or having lots of holes) in the process. However, when researchers replaced arginine with other positively-charged amino acids, it lost its function.
Researchers hope these findings will aid further studies in enhancing the properties of the TAT protein that make it a good vehicles for transporting therapeutic molecules into cells.
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