Navigation Links
Protein structure: Immune system foiled by a hairpin

The innate immune system detects invasive pathogens and activates defense mechanisms to eliminate them. Pathogens, however, employ a variety of tricks to block this process. A new study led by Karl-Peter Hopfner of Ludwig-Maximilians-Universitaet (LMU) in Munich shows how the measles virus thwarts the system, by means of a simple hairpin-like structure.

The innate immune system is the body's first line of defense against invasive pathogens and noxious chemicals. Essentially the system consists of an array of receptors that recognize particular molecular conformations which are characteristic of pathogenic organisms and viruses. Among the classes of molecules bound by these receptors are viral nucleic acids, which are bound specifically by so-called RIG-I-like receptors in the cytoplasm of infected cells. One of these is MDA5, which polymerizes into filaments on long double-stranded RNAs that indicate the presence of RNA viruses. RIG-I itself binds to shorter terminal segments of viral RNAs.

However, viruses have come up with a plethora of ways to avoid triggering immune defense measures. "The virus that causes measles, for instance, produces a so-called V protein, which binds specifically to MDA5 and one other RIG-I-like receptor, and thus impairs recognition of virus-infected cells by the adaptive immune system, although it does not inhibit RIG-I itself," says Professor Karl-Peter Hopfner of LMU's Gene Center. Indeed this kind of competition between viral and cellular proteins largely determines the distribution and - above all - the virulence of viral pathogens.

A hairpin opens up the receptor

"We have been able to crystallize the complex formed by the V protein and MDA5 for the first time, and have determined its three-dimensional structure in detail," Hopfner reports. This structure also permitted Hopfner's team, in collaboration with LMU virologist Professor Karl-Klaus Conzelmann, to clarify the mode of action of the V protein. The analysis revealed that it inserts a hairpin loop into the core secondary structure of MDA5, unfolding the protein and allowing V to bind to a segment that is normally buried in the interior of the molecule. This in turn prevents MDA5 from forming filaments and signaling the presence of viral RNA.

This finding was completely unexpected, and explains why MDA5, but not RIG-I, is inhibited by the V protein: This internal sequence is different in RIG-I and this is the reason why RIG-I is not targeted by the viral product. "Our work provides a detailed insight into the mechanisms viral proteins use to inhibit host protein function. It may also open opportunities for new therapeutic interventions," Hopfner concludes.

Contact: Luise Dirscherl
Ludwig-Maximilians-Universitt Mnchen

Related biology news :

1. How the protein transport machinery in the chloroplasts of higher plants developed
2. Scientists discover structure of protein essential for quality control, nerve function
3. Protein production: Going viral
4. New study defines the long-sought structure of a protein necessary for cell-cell interaction
5. NYU biologists identify proteins vital to chromosome segregation
6. Removing protein garbage in nerve cells may help control 2 neurodegenerative diseases
7. Protein creates paths for growing nerve cells
8. Cholesterol helps regulate key signaling proteins in the cell
9. Cats are able to navigate complex combinations of wet and dry foods to achieve a consistent intake of protein, fat and carbohydrate
10. Researchers identify proteins that indicate which kidney tumors are most likely to spread
11. Protein injection points to muscular dystrophy treatment
Post Your Comments:
(Date:6/2/2016)... 2016 The Department of Transport Management ... 44 million US Dollar project, for the , ... Personalization, Enrolment, and IT Infrastructure , to ... and implementation of Identity Management Solutions. Numerous renowned international vendors ... Decatur was selected for the most compliant and ...
(Date:5/24/2016)... patient care by providing unparalleled technology to leaders of the medical imaging industry.  As ... added to the range of products distributed by Ampronix. Photo - ... ... ... ...
(Date:5/9/2016)... Elevay is currently known as ... for high net worth professionals seeking travel for work ... world, there is still no substitute for a face-to-face ... your deal with a firm handshake. This is why ... of citizenship via investment programs like those offered by ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 23, 2016   Boston Biomedical , an ... designed to target cancer stemness pathways, announced that ... Orphan Drug Designation from the U.S. Food and ... cancer, including gastroesophageal junction (GEJ) cancer. Napabucasin is ... inhibit cancer stemness pathways by targeting STAT3, and ...
(Date:6/23/2016)... Calif. , June 23, 2016  The Prostate Cancer Foundation ... increasingly precise treatments and faster cures for prostate cancer. Members of the Class ... across 15 countries. Read More About the Class of ... ... ...
(Date:6/23/2016)... ... June 23, 2016 , ... In a new case report published ... how a patient who developed lymphedema after being treated for breast cancer benefitted from ... the paradigm for dealing with this debilitating, frequent side effect of cancer treatment. ...
(Date:6/23/2016)... ... June 23, 2016 , ... ClinCapture, the only ... Center and will showcase its product’s latest features from June 26 to June ... scientific poster on Disrupting Clinical Trials in The Cloud during the conference. ...
Breaking Biology Technology: