TAT is not involved in transmitting the HIV virus; it only aids the passage of other materials across the membranes of infected cells. Now, a multidisciplinary team from the University of Illinois involving graduate student Abhijit Mishra, materials science and engineering professor Gerard Wong and postdoctoral researcher Vernita Gordon, has solved this mystery, something that could help improve the design of therapeutic agents that cross a variety of membrane types.
Lead author of the study Gerard Wong said: "TAT is extremely good at getting through cell membranes. You can attach TAT to almost anything and it will drag it across the membrane. It can work for virtually all tissues, including the brain." The TAT protein transduction domain of the HIV virus is a tiny part of the overall TAT protein, containing only 11 amino acids, of which six are arginine, a positively charged amino acid that gives the protein its activity.
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. Keeping these two things in mind, the researchers had thought that any positively charged amino acid could deform the membrane in a way that opened up a pathway through it.
Using confocal microscopy and synchrotron x-ray scattering (SAXS), where the pattern of X-ray scattering can reveal how atomic and nano scale materials are structured, researchers found that adding the TAT protein to a membrane completely altered its SAXS spectrum, a sign that the membrane conformation had changed.
Upon analyzing the spectrum, they noted that TAT had completely reconstructed the membranes and made them porous thus making it easier for other biological processes to bring materials through.