Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

An Atomic-level Look at an HIV Accomplice

23.11.2009
Since the discovery in 2007 that a component of human semen called SEVI boosts infectivity of the virus that causes AIDS, researchers have been trying to learn more about SEVI and how it works, in hopes of thwarting its infection-promoting activity.

Now, scientists at the University of Michigan have determined the atomic-level, three-dimensional structure of a SEVI precursor known as PAP248-286 and discovered how it damages cell membranes to make them more vulnerable to infection with HIV. The work is described in two new papers.

The most recent, describing the structure, was published online Nov. 17 in the Journal of the American Chemical Society. The paper describing how PAP248-286 interacts with cell membranes appeared in the Nov. 4 issue of Biophysical Journal.

PAP248-286 is a peptide---a chain of amino acids not long enough to be considered a protein. Individual PAP248-286 peptides have a tendency to clump together to form amyloid fibers called SEVI (semen enhancer of viral infection). Amyloid fibers are of great interest because they are the calling cards of many neurodegenerative diseases, such as Alzheimer's and Parkinson's, and aging-related diseases like type-2 diabetes. Using NMR (nuclear magnetic resonance) spectroscopy, a technique that not only yields atomic-level details of a molecule's structure, but also shows how the molecule nestles into the membrane with which it interacts, researcher Ayyalusamy Ramamoorthy and coworkers found that the structure of PAP248-286 is unlike that of most other amyloid-forming peptides and proteins.

In solution, SEVI is completely unstructured or has no definite shape and is therefore ineffective. On the other hand, "when bound to the membrane, it's in a spaghetti-like arrangement---a disorganized, loose coil," said Ramamoorthy, a professor of chemistry and of biophysics. In contrast, most other amyloid proteins assume a more ordered, helical configuration. Also unlike other amyloid peptides, SEVI does not penetrate deep into the greasy region of the cell membrane, but is located near the surface. Ramamoorthy and coauthors believe the spread-out, disordered configuration and its location in the cell membrane may explain the ability of SEVI fibers to enhance HIV infection, as the arrangement provides more surface area with which the virus can interact.

A key finding of the second study is that PAP248-286 "shocks" the membrane, inducing a structural change---a kind of dimple that allows HIV to attach to and enter the cell.

Next, Ramamoorthy and colleagues hope to discern more structural details of PAP248-286 and SEVI. They also plan to screen antioxidant compounds such as green tea extract, curcumin and resveratrol (found in red wine) to see if such compounds are capable of blocking SEVI's HIV-enhancing activity.

Ramamoorthy's coauthors on the Journal of the American Chemical Society paper are graduate student Ravi Nanga, post-doctoral fellows Jeffrey Brender and Nataliya Popovych and NMR specialist Subramanian Vivekanandan. His coauthors on the Biophysical Journal paper are Brender, graduate student Kevin Hartman, former post-doctoral fellow Lindsey Gottler, former graduate student Marchello Cavitt and biophysics undergraduate student Daniel Youngstrom.

This research was supported by funds from the National Institutes of Health.

For more information:
Ayyalusamy Ramamoorthy: http://www.ns.umich.edu/htdocs/public/experts/ExpDisplay.php?beginswith=Ramamoorthy

Journal of the American Chemical Society paper, NMR Structure in a Membrane Environment Reveals Putative Amyloidogenic Regions of the SEVI Precursor Peptide PAP248-286

Biophysical Journal paper, Helical Conformation of the SEVI Precursor Peptide PAP248-286, a Dramatic Enhancer of HIV Infectivity, Promotes Lipid Aggregation and Fusion

Nancy Ross-Flanigan | Newswise Science News
Further information:
http://www.cell.com/biophysj/
http://www.umich.edu

More articles from Health and Medicine:

nachricht The FiTS app now offering cooking videos as it expands its concept for long-term behavior modification
18.09.2018 | vitaliberty GmbH

nachricht The microbiota in the intestines fuels tumour growth
18.09.2018 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Patented nanostructure for solar cells: Rough optics, smooth surface

Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.

"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...

Im Focus: New soft coral species discovered in Panama

A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.

Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...

Im Focus: New devices based on rust could reduce excess heat in computers

Physicists explore long-distance information transmission in antiferromagnetic iron oxide

Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.

Im Focus: Finding Nemo's genes

An international team of researchers has mapped Nemo's genome

An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...

Im Focus: Graphene enables clock rates in the terahertz range

Graphene is considered a promising candidate for the nanoelectronics of the future. In theory, it should allow clock rates up to a thousand times faster than today’s silicon-based electronics. Scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) and the University of Duisburg-Essen (UDE), in cooperation with the Max Planck Institute for Polymer Research (MPI-P), have now shown for the first time that graphene can actually convert electronic signals with frequencies in the gigahertz range – which correspond to today’s clock rates – extremely efficiently into signals with several times higher frequency. The researchers present their results in the scientific journal “Nature”.

Graphene – an ultrathin material consisting of a single layer of interlinked carbon atoms – is considered a promising candidate for the nanoelectronics of the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

One of the world’s most prominent strategic forums for global health held in Berlin in October 2018

03.09.2018 | Event News

4th Intelligent Materials - European Symposium on Intelligent Materials

27.08.2018 | Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

 
Latest News

World's first passive anti-frosting surface fights ice with ice

18.09.2018 | Materials Sciences

A novel approach of improving battery performance

18.09.2018 | Materials Sciences

Scientists use artificial neural networks to predict new stable materials

18.09.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>