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Researchers discover how stealthy HIV protein gets into cells
Date:3/17/2008

Scientists have known for more than a decade that a protein associated with the HIV virus is good at crossing cell membranes, but they didnt know how it worked. A multidisciplinary team from the University of Illinois has solved the mystery, and their findings could improve the design of therapeutic agents that cross a variety of membrane types.

A paper describing their findings appears this month in Angewandte Chemie.

The TAT protein transduction domain of the HIV virus has some remarkable properties. First, it is a tiny part of the overall TAT protein, containing only 11 amino acids. Second, and more important, it has an uncanny knack for slipping across membranes, those lipid-rich bags that form the boundaries of cells and cellular components and are designed to keep things out.

TAT is extremely good at getting through cell membranes, said materials science and engineering professor Gerard Wong, who led the new study. 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 proteins versatility makes it desirable as a drug-delivery device. It is already being used for gene therapy. (TAT is not involved in transmitting the HIV virus; it only aids the passage of other materials across the membranes of infected cells.)

Because it has so many potential uses, scientists have long endeavored to understand the mechanism that allows the TAT protein to work. But their efforts have been stymied by some baffling observations.

Six of its 11 residues 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, Wong said. Since opposites attract, it made sen
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Contact: Diana Yates
diya@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

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