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

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



WATERS CORPORATION

Channels

Drug Discovery

view channel
Image: Star-like glial cells in red surround alpha-beta plaques in the cortex of a mouse with a model of Alzheimer\'s disease (Photo courtesy of Strittmatter laboratory/Yale University).

Experimental Cancer Drug Reverses Symptoms in Mouse Model of Alzheimer's Disease

An experimental, but clinically disappointing drug for treatment of cancer has been found to be extremely effective in reversing the symptoms of Alzheimer's disease (AD) in a mouse model.... Read more

Lab Technologies

view channel
Image: The gene assembly robot, the GeneTheatre (Photo courtesy of Analytik Jena AG).

Genomic Research Laboratories Await New Compact Liquid Handling System

A small footprint benchtop liquid handler that automates multiple gene assembly tasks and associated procedures such as PCR setup is now available for use by biotech and genomic research laboratories.... Read more

Business

view channel

NanoString and MD Anderson Collaborate on Development of Novel Multi-Omic Expression Profiling Assays for Cancer

The University of Texas MD Anderson Cancer Center (Houston, TX, USA) and NanoString Technologies, Inc. (Seattle, WA, USA) will partner on development of a revolutionary new type of assay—simultaneously profiling gene and protein expression, initially aiming to discover and validate biomarker signatures for immuno-oncology... Read more
 

Events

27 May 2015 - 28 May 2015
02 Jun 2015 - 03 Jun 2015
15 Jun 2015 - 18 Jun 2015
Copyright © 2000-2015 Globetech Media. All rights reserved.