Navigation Links
Burnham researchers discover 'on switch' for cell death signaling mechanism
Date:1/5/2009

LA JOLLA, Calif., January 5, 2009-- Scientists at Burnham Institute for Medical Research (Burnham) have determined the structure of the interactions between proteins that form the heart of the death inducing signaling complex (DISC), which is responsible for triggering apoptosis (programmed cell death).

The research, performed by Stefan Riedl, Ph.D., and colleagues, published online on Dec. 31 in the journal Nature, highlights how protein-protein interactions between Fas receptor and Fas-associated death domain protein (FADD) mechanistically control DISC formation. The X-ray crystal structure of the Fas-FADD death domain complex revealed a particular arrangement of four FADD death domains bound to four Fas death domains. The structure showed that Fas undergoes a conformational change, creating an open form of the protein that acts as a site for FADD binding and also participates in the association of other Fas molecules in the clustered complex. Dr. Riedl and colleagues propose that Fas opening itself acts as a control switch for DISC formation and initiation of apoptosis.

"We found an explanation for why binding of Fas ligand is not enough to initiate DISC formation and set cell death in motion," said Dr. Riedl. "You need a special arrangement of Fas receptors to trigger opening of the Fas death domain, and only then do you get activation. Another interesting point is that this X-ray crystal structure uncovered a general mechanism for receptor signaling solely by protein clustering. Understanding the initiation of the death inducing signaling complex is of great interest because if you can activate or inhibit cell death you can have a major impact on many diseases such as cancer."

This work, by scientists of the Apoptosis & Cell Death program at the Burnham Cancer Center and their collaborators, sheds the first light on the detailed architecture of this elusive complex. Despite intense efforts by various teams, the nature of the Fas-FADD interactions and their role in DISC signaling had not been directly characterized prior to this study. The X-ray crystal structure now provides detailed information about the Fas-FADD complex at a resolution of 2.7 Angstroms. Electron microscopy studies additionally revealed that incubation of Fas death domain with full-length FADD resulted in the formation of DISC-like structures that clustered together.


'/>"/>

Contact: Josh Baxt
jbaxt@burnham.org
858-795-5236
Burnham Institute
Source:Eurekalert

Related biology news :

1. The Burnham buzz
2. Burnham researchers turn cancer friend into cancer foe
3. Burnham researcher awarded $8 million grant
4. Salk researchers develop novel glioblastoma mouse model
5. New genetic markers for ulcerative colitis identified, researchers report in Nature Genetics
6. The gold standard: Biodesign Institute researchers use nanoparticles to make 3-D DNA nanotubes
7. Researchers engineer pancreatic cell transplants to evade immune response
8. UC Davis researchers find molecule that targets brain tumors
9. UT Public Health researchers find link to severe Staph infections
10. SUNY Downstate researchers find that memory storage molecule preserves complex memories
11. Researchers make breakthrough in the production of double-walled carbon nanotubes
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/13/2016)... 13, 2016 ... of the  "India Biometrics Authentication & ... (2015-2020)"  report to their offering.  ... announced the addition of the  "India ... Estimation & Forecast (2015-2020)"  report ...
(Date:1/8/2016)... MANCHESTER, United Kingdom , Jan. 8, 2016   ... diagnostic products, today announced the closing of a $9 million ... Proceeds from the financing will be used to accelerate the ... for detecting early-stage pressure ulcers. United ... receiving CE Mark approval. The device,s introduction has been met ...
(Date:1/7/2016)... LONDON , Jan. 7, 2016 ... demand for biopharmaceutical products such as biologics and ... pressure to reduce healthcare expenditure, growing demand for ... growing aging population. Biosimilars are similar versions of ... with regards to their quality, safety, and efficacy. ...
Breaking Biology News(10 mins):
(Date:2/3/2016)... N.J. , Feb. 3, 2016 ... totaling more than $1 million for researchers in ... working on health-related research that demonstrates exciting potential. ... round of funding for the New Jersey Health Foundation ... faculty members at these educational institutions— Princeton University, ...
(Date:2/3/2016)... ... 2016 , ... ProMIS Neurosciences is currently in the process ... propagating strains of Amyloid beta involved in Alzheimer’s disease. The Company plans to ... on from the first misfolded Amyloid beta target announced on Nov. 12, 2015, ...
(Date:2/3/2016)... ... February 03, 2016 , ... ... annual report which summarizes and analyzes nearly 750 unique supply chain notifications ... and analysis service. , Supply chain risk management practitioners subscribe to the ...
(Date:2/3/2016)... Feb. 3, 2016  Today, Symphony Technology Group (STG) ... , a leading provider of primary research and analytics-based ... IMS Health , a global information and technology services ... and technologies will be integrated into IMS Health to ... market research capabilities. ...
Breaking Biology Technology: