Features | Partner Sites | Information | LinkXpress
Sign In
PZ HTL SA
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



BIOSIGMA S.R.L.
RANDOX LABORATORIES
SLAS - Society for Laboratory Automation and Screening
comments powered by Disqus

Channels

Drug Discovery

view channel

Omega 3 Found to Improve Behavior in Children with ADHD

Supplements of the fatty acids omega 3 and 6 can help children and adolescents who have a specific kind of have attention deficit hyperactivity disorder (ADHD). Moreover, these findings indicate that a customized cognitive training program can improve problem behavior in children with ADHD. Statistics show that 3%–6%... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Lab Technologies

view channel

e-Incubator Technology Provides Real-Time Imaging of Bioengineered Tissues in a Controlled Unit

A new e-incubator, an innovative miniature incubator that is compatible with magnetic resonance imaging (MRI), enables scientists to grow tissue-engineered constructs under a controlled setting and to study their growth and development in real time without risk of contamination or damage. Offering the potential to test... Read more

Business

view channel

Two Industry Partnerships Initiated to Fuel Neuroscience Research

Faster, more complex neural research is now attainable by combining technology from two research companies. Blackrock Microsystems, LLC (Salt Lake City, UT, USA), a developer of neuroscience research equipment, announced partnerships with two neuroscience research firms—PhenoSys, GmbH (Berlin, Germany) and NAN Instruments, Ltd.... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.