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:1/4/2019)... ... January 03, 2019 , ... Over the last ... their drug discovery research workflows with biology ranging from single cell-type spheroids to ... in vitro studies, they create several challenges that need to be overcome in ...
(Date:12/25/2018)... , ... December 24, 2018 , ... ... The Rockefeller University have discovered a new use for a long-standing computational concept ... spam control, blocking unwanted files and messages. Using blacklisting as a filter to ...
(Date:12/19/2018)... ... , ... InTouchMD’s flagship product, Pulse , has been honored by PM360 ... is featuring the recognition in its 7th annual Innovations issue, created for purpose of ... medical device industries. , “This recognition comes at an exciting time for Pulse as ...
Breaking Biology News(10 mins):
(Date:1/7/2019)... ... January 07, 2019 , ... Kainos Medicine Inc. ... Disease drug candidate, code-named "KM-819." KM-819 is an orally active small molecule ... in South Korea. , This Phase 1 randomized, double-blind, placebo-controlled dose-escalation study ...
(Date:12/20/2018)... ... , ... New Year’s brings reflection and desire to improve for individuals and ... (EU) on the horizon, Jim Kasic, president and CEO of Boulder iQ, suggests five ... Device Regulation (MDR), digital health, and big data are just a few of the ...
(Date:12/18/2018)... ... ... Patients with early stages of breast cancer who undergo partial breast proton ... irradiation, a new study suggests. , Patients with early stage breast cancer — stage ... the cancerous tumor because there is a 30 to 40 percent change the disease ...
(Date:12/13/2018)... ... December 13, 2018 , ... Microbial ... (human) ingredient. This has been part of their strategic plan and an important ... certification creates custom fermentation opportunities for MDG within the $44 Billion human probiotic ...
Breaking Biology Technology: