Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover how stealthy HIV protein gets into cells

19.03.2008
Scientists have known for more than a decade that a protein associated with the HIV virus is good at crossing cell membranes, but they didn’t 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.”

... more about:
»HIV »Membrane »TaT »Wong »acid »amino »arginine »pores

The TAT protein’s 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 sense to the researchers that the positively charged TAT protein would attract the negatively charged head groups on the surface of the membranes. This attraction could deform the membrane in a way that opened up a pathway through it.

If a short, positively charged protein was all that was needed for TAT to work, the researchers thought, then any positively charged amino acid should do the trick. But when they replaced the arginine in the protein with other positively charged amino acids, it lost its function. Clearly, a positive charge was not enough to make it work.

To get a better picture of the interaction of TAT with a variety of membranes, the researchers turned to confocal microscopy and synchrotron x-ray scattering (SAXS). Although sometimes used in biological studies, SAXS is more common to the fields of physics or materials science, where the pattern of X-ray scattering can reveal how atomic and nano scale materials are structured.

The researchers found that adding the TAT protein to a membrane completely altered its SAXS spectrum, a sign that the membrane conformation had changed. After analyzing the spectrum, the researchers found that TAT had made the membranes porous.

“The TAT sequence has completely reconstructed (the membrane) and made it into something that looks a little bit like a sponge with lots of holes in it,” Wong said.

Something about the TAT protein had induced a “saddle splay curvature” in the membrane. This shape resembles a saddle (like that of a Pringles potato chip), giving the openings, or pores, a bi-directional arc like that seen inside a doughnut hole.

The newly formed pores in the membrane were 6 nanometers wide, large enough to allow fairly sizeable proteins or other molecules to slip through. The pores would also make it easier for other biological processes to bring materials through the membrane.

Further analysis showed that the arginine was interacting with the head groups on the membrane lipids in a way that caused the membrane to buckle in two different directions, bringing on the saddle splay curvature that allowed the pores to form.

When another positively charged amino acid, lysine, was used instead of arginine, the protein bent the membrane in one direction only, forming a shape more like a closed cylinder that would not allow materials to pass through.

These findings will aid researchers hoping to enhance the properties of the TAT protein that make it a good vehicle for transporting therapeutic molecules into cells, Wong said.

Wong also is a professor of physics and of bioengineering.

Diana Yates | EurekAlert!
Further information:
http://www.uiuc.edu

Further reports about: HIV Membrane TaT Wong acid amino arginine pores

More articles from Life Sciences:

nachricht The Secret of the Rock Drawings
24.05.2019 | Max-Planck-Institut für Chemie

nachricht Chemical juggling with three particles
24.05.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New studies increase confidence in NASA's measure of Earth's temperature

A new assessment of NASA's record of global temperatures revealed that the agency's estimate of Earth's long-term temperature rise in recent decades is accurate to within less than a tenth of a degree Fahrenheit, providing confidence that past and future research is correctly capturing rising surface temperatures.

The most complete assessment ever of statistical uncertainty within the GISS Surface Temperature Analysis (GISTEMP) data product shows that the annual values...

Im Focus: The geometry of an electron determined for the first time

Physicists at the University of Basel are able to show for the first time how a single electron looks in an artificial atom. A newly developed method enables them to show the probability of an electron being present in a space. This allows improved control of electron spins, which could serve as the smallest information unit in a future quantum computer. The experiments were published in Physical Review Letters and the related theory in Physical Review B.

The spin of an electron is a promising candidate for use as the smallest information unit (qubit) of a quantum computer. Controlling and switching this spin or...

Im Focus: Self-repairing batteries

UTokyo engineers develop a way to create high-capacity long-life batteries

Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...

Im Focus: Quantum Cloud Computing with Self-Check

With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.

Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...

Im Focus: Accelerating quantum technologies with materials processing at the atomic scale

'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.

However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

On Mars, sands shift to a different drum

24.05.2019 | Physics and Astronomy

Piedmont Atlanta first in Georgia to offer new minimally invasive treatment for emphysema

24.05.2019 | Medical Engineering

Chemical juggling with three particles

24.05.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>