Troy, N.Y. - Two theoretical physicists at Rensselaer Polytechnic Institute have uncovered what they believe is the long-sought-after pathway that an HIV peptide takes to enter healthy cells. The theorists analyzed two years of biocomputation and simulation to uncover a surprisingly simple mechanism describing how this protein fragment penetrates the cell membrane. The discovery could help scientists treat other human illnesses by exploiting the same molecules that make HIV so deadly proficient.
The findings are detailed in the Dec. 26, 2007, issue of the Proceedings of the National Academy of Sciences (PNAS).
For the last decade, scientists have known that a positively charged, 11-amino-acid chain of HIV (HIV-1 Tat protein) can do the nearly unthinkable X cross through the cell membrane. Sometimes referred to as an "arrow protein," HIV-1 Tat pierces the cell membrane and carries a cargo though the cell membrane.
Its unique cell-puncturing ability has been the subject of hundreds of scientific articles investigating the type of materials that can piggyback on the peptide and also enter the cell. Researchers have proposed using the peptide to deliver genes for gene therapy and drugs that need to be delivered directly to a cell. But despite many potential medical applications, the actual mechanism that opens the holes in the cell remained undiscovered.
The Rensselaer researchers have discovered that the positively charged HIV peptide is drawn to negatively charged groups inside the cell membrane. When the HIV peptide cannot satisfy itself with the negative charges available on the cell membrane surface it is directly attached to, it reaches through the membrane to grab negatively charged groups in the molecules on the other side, opening a transient hole in the cell.
"What we saw in our computer calculations wasn't at all what we expected to see when we began," said co-lead author and Senior Constella
|Contact: Gabrielle DeMarco|
Rensselaer Polytechnic Institute