When the human body becomes infected with new influenza viruses, the immune system rapidly activates an inborn protective mechanism to inhibit the intruding pathogen. A protein known as Mx plays an important role in this process, keeping the spread of viruses in check.
Exactly how Mx accomplishes this task was previously unknown. Now virologists from the Institute of Medical Microbiology at the Freiburg University Medical Center and structural biologists from the Max Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch, Germany, have unraveled the structure of the Mx protein and are able to explain how it develops its anti-viral effect (Nature, doi: 10.1038/nature08972)*.
New influenza viruses jump from animals to humans with alarming frequency, as evidenced by the H5N1 bird flu virus or, more recently, with the swine flu virus. Although humans usually do not have any preexisting immunity to such pathogens, they are not completely unprotected against the invaders. The human body can rapidly mobilize a defense strategy which prevents the influenza viruses from proliferating unchecked in the body.
An essential element of this protection is a protein, known as Mx (short for myxovirus resistance), produced by the body which recognizes many viruses and prevents them from replicating inside infected cells. Under normal conditions this protective protein is not present in the cell at all, but after infection it can be produced in large quantities. The order to produce this protein Mx is made by the signaling protein interferon, which is excreted by infected cells and alarms the organism of the virus infection.
Mx is a molecular machine which does not develop its full power until the individual molecules have joined to form a ring-structured macromolecular network. A central element of the formation of these ring structures is the special part of Mx known as the stalk.
Scientists have attempted to describe the structure of this stalk for years. The virologists Otto Haller, Alexander von der Malsburg, and Georg Kochs in Freiburg and the structural biologists Oliver Daumke, Song Gao, Susann Paeschke, and Joachim Behlke from MDC in Berlin-Buch have now unraveled the secret of the stalk structure of Mx at the atomic level. This structure explains the composition of Mx and allows scientists to conduct tests to make predictions concerning the mode of action of the antiviral molecule.
In combination with findings from earlier biochemical studies, the results of this study make it clear that the stalk structure of Mx functions as a kind of clamp which restrains and deactivates important components of the influenza virus in the infected cell. The fact that new forms of flu can lead to epidemics or even pandemics in spite of this defense mechanism is due to the power and aggressiveness of these pathogens.
The researchers are confident that their new findings about the protective Mx protein will form the basis for the development of new antiviral drugs for combating dangerous influenza viruses. Moreover, they are also certain that this new knowledge about the function of Mx will increase their understanding of other members of this family of proteins.
*Structural basis of oligomerisaton in the stalk region of dynamin-like MxA
Song Gao1,2, Alexander von der Malsburg3, Susann Paeschke1, Joachim Behlke1, Otto Haller3, Georg Kochs3, Oliver Daumke11Max Delbrück Center for Molecular Medicine, Crystallography, Robert-Rössle-Strasse 10, 13125 Berlin, Germany
3Department of Virology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herderstrasse 11, 79104 Freiburg, Germany
Contact:Dr. Oliver Daumke
How do muscles know what time it is?
21.08.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
A novel synthetic antibody enables conditional “protein knockdown” in vertebrates
20.08.2018 | Technische Universität Dresden
There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.
The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
21.08.2018 | Materials Sciences
20.08.2018 | Information Technology
20.08.2018 | Life Sciences