Navigation Links
Innate immunity
Date:6/4/2013

In animal cells, DNA molecules are normally restricted to the cell nucleus and the mitochondria. When DNA appears outside these organelles in the so-called cytosol - it most probably originates from a bacterial pathogen or a DNA virus. This is why cytosolic DNA triggers a strong response by the innate immune system. However, various types of insult can also lead to the release into the cytosol of the cell's own DNA. In this case, the resulting immune response may precipitate an autoimmune disease.

The innate immune system is the body's first line of defense against invasive pathogens. It reacts to intruders by inducing the production of interferon proteins that alert the adaptive arm of the immune system. However, the protein that recognizes DNA which is "out of place" in the cytosol resisted identification until a short time ago. "It was only recently discovered that the enzyme cGAS serves as the sensor," says Professor Karl-Peter Hopfner of LMU's Genzentrum. Hopfner and his colleagues have now determined the three-dimensional structure of this DNA detector.

Cytosolic DNA activates enzyme

Indeed, as they report in the journal Nature, the LMU researchers not only delineated the structure of the cGAS molecule itself, they also elucidated the conformation of the complex formed when it binds to DNA. Careful analysis of both structures, together with further functional studies carried out in collaboration with Professor Veit Hornung of Bonn University, enabled the scientists to work out how cGAS recognizes, and is activated by, cytosolic DNA. Binding of the DNA alters the structure of cGAS, enabling the enzyme to catalyze the synthesis of a cyclic dinucleotide. This molecule then activates a transmembrane protein, which in turn stimulates the production of interferon. "In a second study, published simultaneously in Nature, we also determined the structure of the dinucleotide, and show that it represents a previously unknown form of this class of signaling molecule," Hornung adds.

To their surprise, the researchers also found that cGAS is structurally and mechanistically related to an antiviral enzyme that triggers an immune response upon detection of foreign RNA in the cytosol. "With this finding we have the first evidence for a mechanistic and evolutionary link between DNA- and RNA-induced immune reactions," Hopfner comments.

The new results are also very interesting from a clinical standpoint, as a better understanding of the interferon response could have implications for therapy, in two respects. On the one hand, targeted stimulation of interferon production could enhance immunotherapies directed against tumors. Conversely, the ability to attenuate misdirected immune responses against the body's own antigens could lead to better treatments for autoimmune conditions.


'/>"/>

Contact: Kathrin Bilgeri
kathrin.bilgeri@lmu.de
49-892-180-6938
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

Related biology news :

1. Innate immune system protein provides a new target in war against bacterial infections
2. UTSW researchers identify new enzyme that acts as innate immunity sensor
3. Innate immunity system of sheep and goat herds against viral infections clarified
4. Flu immunity is affected by how many viruses actually cause the infection
5. Behind closed doors: Researchers show how probiotics boost plant immunity
6. Circuitry of cells involved in immunity, autoimmune diseases exposed
7. Pitt team finds immunity protein that ramps up inflammation, and agents that can block it
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/26/2016)... -- Research and Markets has announced the ...  report to their offering.  , ,     (Logo: ... forecast the global multimodal biometrics market to grow ... 2016-2020.  Multimodal biometrics is being implemented ... healthcare, BFSI, transportation, automotive, and government for controlling ...
(Date:4/13/2016)... 13, 2016  IMPOWER physicians supporting Medicaid patients in ... new clinical standard in telehealth thanks to a new ... higi platform, IMPOWER patients can routinely track key health ... mass index, and, when they opt in, share them ... to a local retail location at no cost. By ...
(Date:3/22/2016)... March 22, 2016 ... Sensors Market for Consumer Industry by Type (Image, ... Application (Communication & IT, Entertainment, Home Appliances, ... Forecast to 2022", published by MarketsandMarkets, the ... to reach USD 26.76 Billion by 2022, ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... - FACIT has announced the creation of a ... Propellon Therapeutics Inc. ("Propellon" or "the Company"), to ... of first-in-class WDR5 inhibitors for the treatment of ... an exciting class of therapies, possessing the potential ... patients. Substantial advances have been achieved with the ...
(Date:6/23/2016)... YORK , June, 23, 2016  The Biodesign ... to envision new ways to harness living systems and ... Modern Art (MoMA) in New York City ... than 130 participating students, showcased projects at MoMA,s Celeste ... Paola Antonelli , MoMA,s senior curator of architecture ...
(Date:6/23/2016)... LOUISVILLE, Ky. , June 23, 2016 /PRNewswire/ ... from two Phase 1 clinical trials of its ... double-blind, placebo-controlled, single and multiple ascending dose studies ... and pharmacodynamics (PD) of subcutaneous injection in healthy ... APL-2 subcutaneously (SC) either as a single dose ...
(Date:6/23/2016)... ... 23, 2016 , ... Regulatory Compliance Associates® Inc. (RCA), a ... webinar on Performing Quality Investigations: Getting to Root Cause. This ... charge. , Incomplete investigations are still a major concern to the Regulatory Authorities ...
Breaking Biology Technology: