Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How Proteins Talk to Each Other

23.09.2009
Caspase-3 Cleaves in Unforeseen Ways

Investigators at Burnham Institute for Medical Research (Burnham) have identified novel cleavage sites for the enzyme caspase-3 (an enzyme that proteolytically cleaves target proteins).

Using an advanced proteomic technique called N-terminomics, Guy Salvesen, Ph.D., professor and director of the Apoptosis and Cell Death Research program of Burnham’s NCI-designated Cancer Center, and colleagues determined the cleavage sites on target proteins and found, contrary to previous understanding, that caspase-3 targets á-helices as well as unstructured loops. In addition, researchers found that caspase-3 and the substrates it binds to co-evolved. The paper was published on September 20 in the journal Nature Structural & Molecular Biology.

Prior to this study, scientists believed that proteases primarily cleave in unstructured loops, unstable parts of proteins that are readily accessible. The discovery that caspase-3 also cleaves á-helices contradicts a current dogma and offers new insights into protein signaling pathways.

“This was a big surprise because there shouldn’t be anything for a protease to grab onto in a helix,” said Dr. Salvesen. “We found that the basic concept that they don’t cleave to helices is wrong. However, though we’ve found that proteases can cleave helices, we don’t believe that’s their biological function.”

In addition to determining cleavage sites, the team also determined which interactions were “biologically significant.” In other words which cleavages altered the function of the target protein and which ones had little impact.

The team tested the human caspase-3 and the Staphylococcal protease glutamyl endopeptidase (GluC) against the Escherichia coli (E. coli) proteosome. In a second set, the human caspase substrate was challenged with human caspase-3 . The researchers found cleavage sites using N-terminal proteomics (N-terminomics), in which cleaved substrates are tagged at an exposed edge (N-terminal) and analyzed though mass spectrometry. The data from these assays were then matched against lists of substrates in the Protein Data Bank. Notably, caspase-3 did not cleave E. coli proteins as effectively as it did human proteins. However, when hybrid human/E. coli proteins were constructed, cleavage was greatly improved, leading researchers to conclude that caspase-3 co-evolved with its human substrates.

Because they alter the functions of other proteins, proteases like caspase-3 are critical to cell signaling. Understanding how and where they interface with target proteins enhances our ability to understand the progress of diseases.

About Burnham Institute for Medical Research
Burnham Institute for Medical Research is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The institute ranks among the top four institutions nationally for NIH grant funding and among the top 25 organizations worldwide for its research impact. For the past decade (1999-2009), Burnham ranked first worldwide in the fields of biology and biochemistry for the impact of its research publications (defined by citations per publication), according to the Institute for Scientific Information.

Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Burnham is a nonprofit public benefit corporation.

Josh Baxt | EurekAlert!
Further information:
http://www.burnham.org
http://www.burnham.org/default.asp?contentID=779

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>