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:11/19/2015)... YORK , Nov. 19, 2015  Although some ... market is dominated by a few companies, according to ... companies own 51% of the market share of the ... The World Market for Molecular Diagnostic s ... "The market is still controlled by one company ...
(Date:11/17/2015)... LIVERMORE, Calif. , Nov. 17, 2015  Vigilant ... has joined its Board of Directors. ... Vigilant,s Board after recently retiring from the partnership at ... owning 107 companies with over $140 Billion in revenue.  ... performance improvement across all the TPG companies, from 1997 ...
(Date:11/12/2015)... , Nov. 11, 2015   Growing need ... analytical tools has been paving the way for ... determination of discrete analytes in clinical, agricultural, environmental, ... being predominantly used in medical applications, however, their ... sectors due to continuous emphasis on improving product ...
Breaking Biology News(10 mins):
(Date:11/27/2015)... (PRWEB) , ... November 27, 2015 , ... ... Program that includes over 2,000 technical presentations offered in symposia, oral sessions, ... and applied spectroscopy, covers a wide range of applications such as, but not ...
(Date:11/25/2015)... ANNAPOLIS, Md. , Nov. 25, 2015  PharmAthene, ... of Directors has adopted a stockholder rights plan (Rights ... its net operating loss carryforwards (NOLs) under Section 382 ... --> --> PharmAthene,s use of its ... an "ownership change" as defined in Section 382 of ...
(Date:11/25/2015)... QUEBEC CITY , Nov. 25, 2015 /PRNewswire/ ... "Company"), affirms that its business and prospects remain ... , Zoptrex™ (zoptarelin doxorubicin) recently received DSMB ... program to completion following review of the final ... met Phase 2 Primary Endpoint in men with ...
(Date:11/24/2015)... 24, 2015  Asia-Pacific (APAC) holds the third-largest ... market. The trend of outsourcing to low-cost locations ... higher volume share for the region in the ... margins in the CRO industry will improve. ... ( ), finds that the market earned ...
Breaking Biology Technology: