Chemists Discover Proton Mechanism Used by Flu Virus to Infect Cells

The findings are published in the Oct. 22 issue of the journal Science.

Hong, an Iowa State professor of chemistry and an associate of the U.S. Department of Energy¡¯s Ames Laboratory, said her research team used solid-state nuclear magnetic resonance (NMR) spectroscopy to determine the structure and workings of the proton channel that connects the flu virus to a healthy cell.

She said a full understanding of that mechanism could help medical researchers design drugs that stop protons from moving through the channel.

That proton channel is an important part of the life cycle of a flu virus. The virus begins an infection by attaching itself to a healthy cell. The healthy cell surrounds the virus and takes it inside through a process called endocytosis. Once inside the cell, the virus uses a protein called M2 to open a channel. Protons from the healthy cell flow through the channel into the virus and raise its acidity. That triggers the release of the virus¡¯ genetic material into the healthy cell. The virus then hijacks the healthy cell¡¯s resources to replicate itself.

Hong and her research team ¨C Fanghao Hu, an Iowa State doctoral student in chemistry; and Wenbin Luo, a former Iowa State doctoral student who is now a spectroscopist research associate at Penn State University ¨C focused their attention on the structure and dynamics of the proton-selective amino acid residue, a histidine in the transmembrane part of the protein, to determine how the channel conducts protons. Their work was supported by grants from the National Science Foundation and the National Institutes of Health.

Two models had been proposed for the proton-conducting mechanism:

¡ñ A ¡°shutter¡± channel that expands at the charged histidine because of electrostatic repulsion, thus allowing a continuous hydrogen-bonded water chain that takes protons into the virus.

¡ñ Or a ¡°shuttle¡± model featuring histidine rings that rearrange their structure in some way to capture protons and relay them inside.

Hong¡¯s research team found that the histidine rings reorient by 45 degrees more than 50,000 times per second in the open state, but are immobile in the closed state. The energy barrier for the open-state ring motion agrees well with the energy barrier for proton conduction, which suggests that the M2 channel dynamically shuttles the protons into the virus. The chemists also found that the histidine residue forms multiple hydrogen bonds with water, which helps it to dissociate the extra proton.

¡°The histidine acts like a shuttle,¡± Hong said. ¡°It picks up a proton from the exterior and flips to let it get off to the interior.¡±

The project not only provided atomic details of the proton-conducting apparatus of the flu virus, but also demonstrated the abilities of solid-state NMR.

¡°The structural information obtained here is largely invisible to conventional high-resolution techniques,¡± the researchers wrote in their Science paper, ¡°and demonstrates the ability of solid-state NMR to elucidate functionally important membrane protein dynamics and chemistry.¡±

Mei Hong, Chemistry and Ames Laboratory, 515-294-3521, mhong@iastate.edu
Mike Krapfl, News Service, 515-294-4917, mkrapfl@iastate.edu

Media Contact

Mike Krapfl Newswise Science News

More Information:

http://www.iastate.edu

All latest news from the category: Life Sciences and Chemistry

Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to home

Comments (0)

Write a comment

Newest articles

Lighting up the future

New multidisciplinary research from the University of St Andrews could lead to more efficient televisions, computer screens and lighting. Researchers at the Organic Semiconductor Centre in the School of Physics and…

Researchers crack sugarcane’s complex genetic code

Sweet success: Scientists created a highly accurate reference genome for one of the most important modern crops and found a rare example of how genes confer disease resistance in plants….

Evolution of the most powerful ocean current on Earth

The Antarctic Circumpolar Current plays an important part in global overturning circulation, the exchange of heat and CO2 between the ocean and atmosphere, and the stability of Antarctica’s ice sheets….

Partners & Sponsors