Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biologists visualize protein interaction that may initiate viral infection

10.02.2006


Biologists at Purdue University have taken a "snapshot" of a Velcro-like protein on a cell’s surface just after it attached to the dengue virus, a linkup thought to initiate the early stages of infection.


This composite image depicts a "snapshot" of a Velcro-like protein on a cell’s surface just after it attached to the dengue virus, a linkup thought to initiate the early stages of infection.(Graphic/Department of Biological Sciences, Purdue University)



The virus, which is spread by mosquitoes, infects more than 50 million people annually, killing about 24,000 each year, primarily in tropical regions.

During the earliest stages of infection, the dengue virus attaches to the "carbohydrate recognition domain," or CRD, of a key binding protein called DC-SIGN, located on a host cell’s surface.


Using a powerful imaging tool called cryo-electron microscopy, the biologists took a picture of the virus attached to the CRD shortly after the two joined together. It is the first time scientists have visualized the virus and CRD binding.

"We formed the virus-CRD complex, took a snapshot and determined its structure," said Michael Rossmann, the Hanley Distinguished Professor of Biological Sciences in Purdue’s College of Science. "Ultimately, researchers might want to find ways to treat or prevent viral infections, but in order to do that we first have to learn how viruses work and how they initiate infection."

The findings are detailed in a research paper to appear on Feb. 10 in the journal Cell. The research was carried out by Elena Pokidysheva and Ying Zhang, post-doctoral research associates working with Rossmann and Richard J. Kuhn, a professor and head of Purdue’s Department of Biological Sciences.

Researchers from the Howard Hughes Medical Institute at Columbia University provided a cloned gene that enabled the Purdue scientists to produce the CRD.

The CRD is part of a protein receptor molecule called DC-SIGN - or dendritic cell-specific ICAM3 grabbing non-integrin. ICAM stands for intercellular adhesion molecule, a family of cell proteins that viruses bind to, and the number 3 defines a specific protein.

"The binding occurs on dendritic cells, which are usually one of the first lines of defense in the immune system," Kuhn said. "The first step in a virus infecting a cell is usually the attachment of the virus to the receptor. That’s essentially what we are looking at, except in this case, instead of having the receptor, which is normally bound or attached to the cell, we have just a portion of the receptor, the CRD, which we produced separately."

Dengue belongs to a family of viruses known as flaviviruses, which includes a number of dangerous insect-borne diseases such as West Nile, yellow fever and St. Louis encephalitis. These diseases, however, use different biological mechanisms than dengue to infect host cells. Dengue is prevalent in Southeast Asia, Central America and South America. Mosquitoes transmit the virus to people, setting in motion the infection process.

"We and others think that this CRD acts sort of like Velcro to get the virus to stick to the surface of the cell, although this has not been proven," Kuhn said. "Once the virus and protein receptor are linked, perhaps the virus then moves across the cell surface to find a second protein, attaching to that receptor and entering the cell.

"One of the things that this study shows is that only a very small portion of the cell’s surface is occupied by the DC-SIGN molecule, which means a significant amount of space is still available for that other receptor protein that people don’t know about yet."

Zhang said that the initial binding of the CRD and the virus might result in a "signaling event between the DC-SIGN molecule and the other primary receptor, leading to activating the other protein and promoting the cell for infection."

The virus has a diameter of 50 nanometers, or billionths of a meter, and the CRD is 3 nanometers wide.

In cryo-electron microscopy, specimens are first frozen before they are studied with an electron microscope. The method enables scientists to study details as small as 8 angstroms, or .8 nanometers, resolution high enough to see groups of atoms. An angstrom is one ten-billionth of a meter, or roughly a millionth as wide as a human hair.

Zhang discovered that the CRD attaches to a structure on the virus surface that contains two carbohydrates a distance of 18 angstroms apart. This feature apparently is essential for the binding to take place, she said.

"Why doesn’t the binding happen at other sugar-binding sites?" she asked. "The answer is that we need two carbohydrate sites that are 18 angstroms apart. There are no other sites that are 18 angstroms apart."

Each virus particle contains 60 of the features, each having two carbohydrates 18 angstroms apart, representing 60 potential binding sites for the CRD.

Emil Venere | EurekAlert!
Further information:
http://www.purdue.edu

More articles from Life Sciences:

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>