Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biologists see combined structure of cold virus and receptor molecule

13.07.2005


Biologists at Purdue University have determined the combined structure of a common-cold virus attached to a molecule that enables the virus to infect its host, information that ultimately may help researchers develop methods for treating certain viral infections.


This composite image shows the combined structure of Coxsackievirus A21 and a "receptor molecule" called ICAM-1, or intracellular adhesion molecule 1. The virus is one of the viruses that causes the common cold, and the receptor molecule enables the virus to attach to and infect host cells. ICAM-1, located on the surfaces of cells, is represented in blue, and the virus is represented as red. Researchers at Purdue University have determined the structure of the virus-molecule complex by combining images taken using X-ray crystallography and cryo-electron microscopy. Being able to determine the combined structure of the virus and ICAM-1 may teach scientists how the virus recognizes the molecule and how it then anchors to the cell, which represents the initial stages of infection. The virus-molecule complex in the center of this image is a thousandth as wide as a human hair. (Graphic/Department of Biological Sciences, Purdue University)



Coxsackievirus A21 infects host cells first by recognizing a "receptor molecule" called ICAM-1, which is located on the cell’s surface, and then by anchoring itself to the molecule. ICAM-1 stands for intracellular adhesion molecule 1.

"ICAM-1 is the same receptor molecule used by the vast majority of viruses that cause the common cold," said Chuan Xiao, a doctoral student who is leading the research in the laboratory of Michael Rossmann, the Hanley Distinguished Professor of Biological Sciences in Purdue’s College of Science.


Findings will appear in the July issue of the journal Structure.

"The real objective of this work is to study the whole complex of ICAM-1 and the virus as a single entity," Rossmann said. "Being able to characterize the combined structure of the virus and ICAM-1 will teach us how the virus recognizes a particular kind of molecule and how it then anchors to the cell, which represents the initial stages of infection."

Ultimately, researchers are trying to learn more about the binding mechanisms because such knowledge might eventually lead to new treatments.

"One of the many different ways of inhibiting viral infection is to stop the virus from binding to cells," Rossmann said. "That has not been our objective in this case. We just want to learn how this virus infects its host cell. In other words, how does the virus get into the host?"

Coxsackievirus A21 is one of several viruses that cause the common cold.

The researchers used two methods to learn the structure of the virus-molecule complex. One method, a technique called X-ray crystallography, yielded images of the virus with a resolution of 2.5 angstroms, which is nearly fine enough to see individual atoms. Using this technique, researchers create crystals of a substance, in this case the virus. Then, X-rays are passed through the crystals, creating a "diffraction pattern" that can be interpreted with various computational procedures to produce an image.

The other method, a powerful imaging tool called cryo-electron microscopy, was used to determine the entire three-dimensional structure of the virus-molecule complex. With this technique, specimens are first frozen before they are studied with an electron microscope. Cryo-electron microscopy enables scientists to study details as small as 8 angstroms, 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.

"The electron microscopy is necessary for studying the entire complex because you can’t crystallize the complex of ICAM-1 and the virus," Rossmann said. "That’s because crystallization often takes days, weeks or months, but the complex is only stable for hours, which means it doesn’t stay together long enough to crystallize."

The researchers pieced together the overall structure of the virus and ICAM-1 by combining the high-resolution X-ray crystallography images of the virus with the lower resolution electron microscope view.

The findings represent the first time researchers have seen fine details of the complex’s structure.

"It’s important to see the shape of the complex because that could tell us how the virus recognizes the host cell," Rossmann said. "Knowing the structure might also reveal the initial stages of what happens after attachment, and indeed there probably are different steps in the attachment process.

"The receptor apparently binds into what we call a canyon, which is a surface depression on the virus, and it might do that in at least two different steps. Perhaps it binds once loosely on the surface, and then it might bind again deeply into the canyon to strengthen its attachment."

The research paper was written by Xiao; Carol M. Bator-Kelly, a technical assistant in Rossmann’s lab; Elizabeth Rieder, a technical assistant for Eckard Wimmer, a virologist at the State University of New York at Stony Brook; Paul R. Chipman, an electron microscopist at Purdue; Alister Craig, a researcher from the Liverpool School of Tropical Medicine in the United Kingdom; Richard J. Kuhn, a professor of biological sciences at Purdue; Wimmer; and Rossmann.

The images are revealing new details about how amino acids, which are the building blocks of proteins, interact during the binding of Coxsackievirus A21 and ICAM-1.

"In general, some amino acids have a positive charge, and some have a negative charge, and these opposite charges can play a critical role in attracting a virus to a host cell," Rossmann said. "It turns out the attraction between negative and positive charges on the virus and on the host cell seem to be a dominating feature but not the entire story of the recognition process.

"There is also shape involved, and the canyon on the virus and features on the ICAM-1 molecule have to match each other, like a key going into a keyhole."

The research has been funded primarily through a grant from the National Institutes of Health.

Xiao said the research is ongoing, and future work may delve into how Coxsackievirus A21 binds to another cell-receptor molecule called DAF, or decay acceleration factor. The virus binds to both ICAM-1 and DAF at the same time, so future work may result in finding the structure of a complex that includes both molecules attached to the virus.

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

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>