Navigation Links
Burnham researchers discover 'on switch' for cell death signaling mechanism

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
Burnham Institute

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:
(Date:10/29/2015)...   MedNet Solutions , an innovative SaaS-based eClinical ... research, is pleased to announce that it has been ... one of only three finalists for a 2015 ... Growing" category. The Tekne Awards honor Minnesota ... innovation and leadership. iMedNet™ eClinical ...
(Date:10/29/2015)... , Oct. 29, 2015  Rubicon Genomics, ... for U.S. distribution of its DNA library preparation ... and Rubicon,s new ThruPLEX Plasma-seq kit. ThruPLEX Plasma-seq ... the preparation of NGS libraries for liquid biopsies--the ... diagnostic and prognostic applications in cancer and other ...
(Date:10/29/2015)... , Oct. 29, 2015 Today, ... announced a partnership with 2XU, a global leader ... deliver a smart hat with advanced bio-sensing technology. ... other athletes to monitor key biometrics to improve ... strategic partnership, the two companies will bring together the ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... 2015 Orexigen® Therapeutics, Inc. (Nasdaq: OREX ... fireside chat discussion at the Piper Jaffray 27th Annual ... The discussion is scheduled for Wednesday, December 2, at ... A replay will be available for 14 days after ... Julie NormartVP, Corporate Communications and Business Development , BrewLife(858) ...
(Date:11/24/2015)... ... November 24, 2015 , ... The United States Golf ... the 2016 USGA Green Section Award. Presented annually since 1961, the USGA Green Section ... her work with turfgrass. , Clarke, of Iselin, N.J., is an extension ...
(Date:11/24/2015)... ... November 24, 2015 , ... ... But unless it is bound to proteins, copper is also toxic to cells. ... at Worcester Polytechnic Institute (WPI) will conduct a systematic study of copper in ...
(Date:11/24/2015)... -- --> --> ... Market by Product & Services (Primer, Probe, Custom Oligos, ... End-User (Research, Pharmaceutical & Biotech, Diagnostic Labs) - Global ... expected to reach USD 1,918.6 Million by 2020 from ... 10.1% during the forecast period. Browse 183 ...
Breaking Biology Technology: