Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

X-Ray Crystallography Reveals the Two Faces of Flavivirus Nonstructural Protein

By BiotechDaily International staff writers
Posted on 17 Feb 2014
Image: The external face of the Flavivirus NS1 protein (sugars in grey balls) is exposed on infected cell surfaces where it can interact with the immune system. This face is also exposed in secreted NS1 particles present in patient sera. The background image shows artificial membranes coated with the NS1 protein (Photo courtesy of the University of Michigan).
Image: The external face of the Flavivirus NS1 protein (sugars in grey balls) is exposed on infected cell surfaces where it can interact with the immune system. This face is also exposed in secreted NS1 particles present in patient sera. The background image shows artificial membranes coated with the NS1 protein (Photo courtesy of the University of Michigan).
High-resolution X-ray crystallography and electron microscopy have revealed that the Flavivirus NS1 (nonstructural protein 1) has two distinct faces, one that interacts with the interior of the infected host cell and the other that is exposed to antiviral elements in the host's immune system.

Flaviviruses are responsible for several severe diseases of humans including dengue fever, West Nile fever, tick-borne encephalitis, and yellow fever. All the flaviviruses produce nonstructural protein 1 (NS1), which functions in genome replication as an intracellular dimer and in immune system evasion as a secreted hexamer. In general, nonstructural proteins are encoded by the viral genome and are produced in the organisms they infect, but are not packaged into the virus particles. Some of these proteins may play roles within the infected cell during virus replication or act in regulation of virus replication or virus assembly.

Investigators at the University of Michigan (Ann Arbor, USA) and colleagues at Purdue University (Lafayette, IN, USA) chose X-ray crystallography as an approach to developing a better understanding of how NS1 functions.

The investigators isolated and crystallized NS1 from Dengue virus and West Nile virus. They then created a three-dimensional atomic structure map of the protein crystals based on data obtained from X-ray crystallography carried out at the Advanced Photon Source at the Argonne National Laboratory (Illinois, USA). Subsequently, electron microscopy was used to elucidate how NS1 associated with membranes of infected cells.

The investigators reported the crystal structures for full-length, glycosylated NS1 from West Nile and dengue viruses in the February 6, 2014, online edition of the journal Science. Their results revealed that the NS1 hexamer in crystal structures was similar to a solution hexamer visualized by single-particle electron microscopy. Recombinant NS1 bound to lipid bilayers and remodeled large liposomes into lipoprotein nanoparticles. The NS1 structures revealed distinct domains for membrane association of the dimer and interactions with the immune system, and will form a basis for elucidating the molecular mechanism of NS1 function.

"Isolating the protein in order to study it has been a challenge for researchers," said senior author Dr. Janet Smith, professor of biological chemistry at the University of Michigan. "Once we discovered how to do that, it crystallized beautifully. Seeing the design of this key protein provides a target for a potential vaccine or even a therapeutic drug."

"The two faces of NS1 define the regions responsible for its two major functions," said Dr. Smith. "This understanding will guide future research into dissecting and targeting these regions in disease treatment or prevention. We are now collaborating with the Purdue virologists to understand exactly how the two faces of NS1 help the virus survive and thrive in patients. These studies are the next steps toward a vaccine or an antiviral drug."

Related Links:

University of Michigan
Purdue University
Argonne National Laboratory



Channels

Drug Discovery

view channel

Curcumin Used to Treat Alzheimer’s Disease

Curcumin, a natural substance found in the spice turmeric, has been used by many Asian cultures for centuries. Now, new research suggests that a close chemical analog of curcumin has properties that may make it useful as a treatment for Alzheimer’s disease. “Curcumin has demonstrated ability to enter the brain, bind... Read more

Biochemistry

view channel
Image: Induced pluripotent stem (iPS) cells, which act very much like embryonic stem cells, are shown growing into heart cells (blue) and nerve cells (green) (Photo courtesy of Gladstone Institutes/Chris Goodfellow).

Methodology Devised to Improve Stem Cell Reprogramming

In a study that provides scientists with a critical new determination of stem cell development and its role in disease, researchers have established a first-of-its-kind approach that outlines the stages... Read more

Therapeutics

view channel
Image: Cancer cells infected with tumor-targeted oncolytic virus (red). Green indicates alpha-tubulin, a cell skeleton protein. Blue is DNA in the cancer cell nuclei (Photo courtesy of Dr. Rathi Gangeswaran, Bart’s Cancer Institute).

Innovative “Viro-Immunotherapy” Designed to Kill Breast Cancer Cells

A leading scientist has devised a new treatment that employs viruses to kill breast cancer cells. The research could lead to a promising “viro-immunotherapy” for patients with triple-negative breast cancer,... Read more

Lab Technologies

view channel
Image: MIT researchers have designed a microfluidic device that allows them to precisely trap pairs of cells (one red, one green) and observe how they interact over time (Photo courtesy of Burak Dura, MIT).

New Device Designed to See Communication between Immune Cells

The immune system is a complicated network of many different cells working together to defend against invaders. Effectively combating an infection depends on the interactions between these cells.... Read more

Business

view channel

Program Designed to Provide High-Performance Computing Cluster Systems for Bioinformatics Research

Dedicated Computing (Waukesha, WI, USA), a global technology company, reported that it will be participating in the Intel Cluster Ready program to deliver integrated high-performance computing cluster solutions to the life sciences market. Powered by Intel Xeon processors, Dedicated Computing is providing a range of... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.