Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers discover how stealthy HIV protein gets into cells

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:

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

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>