Navigation Links
Biologists visualize protein interaction that may initiate viral infection

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.

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 usual ly 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.


'"/>

Source:Purdue University


Related biology news :

1. Biologists discover why 10% of Europeans are safe from HIV
2. Biologists determine genetic blueprint of social amoeba
3. Biologists Crack Genetic Code for Specialized Spider Silk
4. Biologists discover new pathway into plant cells
5. Biologists develop genome-wide map of miRNA-mRNA interactions
6. How healthy is that marsh? Biologists count parasites
7. Biologists find regions of rice domestication
8. Biologists probe the machinery of cellular protein factories
9. Biologists call for better choice of model organisms in evo-devo
10. Biologists produce global map of plant biodiversity
11. Biologists prove critical step in membrane fusion
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/8/2017)... (NASDAQ: AWRE ), a leading supplier of biometrics ... and year ended December 31, 2016. Revenue ... to $6.9 million in the same quarter last year. Operating ... compared to $2.6 million in the fourth quarter of 2015. ... million, or $0.02 per diluted share, which compares to $1.8 ...
(Date:2/7/2017)... Feb. 7, 2017 Zimmer Biomet Holdings, Inc. ... healthcare, will present at the LEERINK Partners 6th Annual ... Hotel on Wednesday, February 15, 2017 at 10 a.m. ... the presentation can be accessed at http://wsw.com/webcast/leerink28/zbh .  ... conference via Zimmer Biomet,s Investor Relations website at ...
(Date:2/2/2017)... 2, 2017   TapImmune, Inc. (NASDAQ: ... specializing in the development of innovative peptide and ... cancer and metastatic disease, announced today it has ... of a second clinical lot of TPIV 200, ... alpha. The manufactured vaccine product will be used ...
Breaking Biology News(10 mins):
(Date:2/22/2017)... LOS ANGELES, CA (PRWEB) , ... February 22, ... ... company, today announced that is has acquired Kendall Research Systems, LLC ... of Technology (MIT) that develops neural interface technology for research and clinical applications. ...
(Date:2/22/2017)... DIEGO , Feb. 22, 2017  PrimeVax Immuno-Oncology, ... will be presenting at the Annual Biocom Global Life ... March 2, at 11:15 AM, at the Torrey Pines ... thankful to the organizers at Biocom who have chosen ... international symposium of biotechnology companies, investors, and clinical researchers," ...
(Date:2/22/2017)... ... February 22, 2017 , ... ... the leading medical education provider of women’s health, primary care, and specialty ... Council for Continuing Medical Education (ACCME). ACCME’s Accreditation with Commendation is a ...
(Date:2/22/2017)... ... February 22, 2017 , ... LabRoots , the ... around the world, is pleased to announce the 2nd annual Precision Medicine Virtual ... premier, online-only conference focused on the development and advancements in precision medicine. , ...
Breaking Biology Technology: