Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bonding together to fight HIV

25.11.2013
A collaborative team led by a Northeastern University professor may have altered the way we look at drug development for HIV by uncovering some unusual properties of a human protein called APOBEC3G (A3G).

In an article published in Nature Chemistry, Prof. Mark Williams and his graduate student Kathy Chaurasiya, along with several collaborators, show how these unusual properties help us to fight HIV infection.

APOBEC3G

It is well known that in response to virus infection, the body makes specific antibodies to counteract the infection. However, we are also born with another way to fight infection, namely through the action of defense proteins that are always present in our system. These proteins provide the first line of defense against invading pathogens. For example, we are all potentially protected against HIV because we have an antiviral protein called A3G. However, HIV has evolved a strategy to circumvent the activity of this protein by tricking our cells into destroying our own A3G proteins. This is where Prof. Williams's research comes into play.

A MULTI-FUNCTIONAL PROTEIN

A3G moves along a DNA strand as part of its function as an enzyme, and when it reaches a particular one of the four bases in DNA, it chemically alters the DNA, causing HIV to mutate. This was originally thought to be the only way A3G blocks HIV infection. However, some researchers found that even when A3G could not chemically alter the DNA, it still inhibited HIV. To explain this, Prof. Williams's collaborator Dr. Judith Levin from NIH, together with postdoctoral fellow Dr. Yasumasa Iwatani, proposed that A3G forms a roadblock that prevents the virus from making a DNA copy of its genome, thereby stopping HIV replication. This would require A3G to be more slow-acting, yet because the protein normally has to move fast to perform its chemical function, there seemed to be an apparent contradiction in the experimental results.

Professor Williams' research resolves this paradox and shows that the A3G protein does not always have the rapid movement needed for chemical function. Instead, its activity changes over time. "First, A3G is a really fast protein," said Williams. "Then, gradually over time, it becomes a slow protein and remains bound to the DNA, blocking replication."

CHALLENGING POPULAR OPINION

Many researchers doubted that a protein could have both enzyme and roadblock functions. An enzyme is designed to act rapidly, so the idea of the A3G protein starting off fast, and then gradually slowing down seemed physically impossible. Professor Williams' collaborator Dr. Ioulia Rouzina from the University of Minnesota came up with the novel idea that when A3G proteins group together, they become slower over time. To test the idea, the Williams lab used an instrument called optical tweezers that allowed them to stretch single DNA molecules with A3G proteins bound. By measuring the change in DNA length over time as the proteins came on and off the DNA, they could show that the rates at which A3G bound to DNA became slower over time.

How does this happen? It was already known that A3G proteins bind to each other and form a multi-protein complex. "Once the complex is formed, the A3G proteins are no longer able to move rapidly along the DNA strand as needed for chemical modification of the DNA," said Williams. "This suggests that slow binding can also block HIV replication."

IMPACT ON HIV RESEARCH

The A3G protein has at least two mechanisms by which it can block HIV replication. We have known for over 10 years that A3G can, in principle, provide protection from HIV. However, finding a drug that can counter the anti-A3G activity of the virus has been elusive. This new work has the potential to develop alternative approaches to HIV therapy and development of drugs that can enhance the roadblock activity of A3G. This provides an alternate pathway for drug development that has not previously been pursued.

In addition to members of Professor Williams' laboratory at Northeastern University, other researchers contributing to this work included members of the laboratories of Professor Karin Musier-Forsyth at The Ohio State University, Dr. Judith Levin at the NIH, and Dr. Yasumasa Iwatani at Nagoya Medical Center.

This research was generously supported by funding from the National Science Foundation and from the extramural and intramural programs at the NIH.

Lori Lennon | EurekAlert!
Further information:
http://www.neu.edu

Further reports about: DNA DNA molecule DNA strand G proteins HIV HIV infection NIH optical tweezer

More articles from Life Sciences:

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

nachricht Pollen taxi for bacteria
18.07.2018 | Technische Universität München

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Machine-learning predicted a superhard and high-energy-density tungsten nitride

18.07.2018 | Materials Sciences

NYSCF researchers develop novel bioengineering technique for personalized bone grafts

18.07.2018 | Life Sciences

Why might reading make myopic?

18.07.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>