Navigation Links
How proteins talk to each other
Date:9/21/2009

LA JOLLA, Calif., September 21, 2009 -- 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 α-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 α-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.


'/>"/>

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

Related biology news :

1. Researchers prolong the half-life of biopharmaceutical proteins
2. When proteins change partners
3. Disrupting a destructive duo: U of T Mississauga researchers inhibit cancer proteins
4. Bionanomachines -- proteins as resistance fighters
5. Proteins in gel
6. Targeting helpers of heat shock proteins could help treat cancer, cardiovascular disease
7. TRAPping proteins that work together inside living cells
8. Pliable proteins keep photosynthesis on the light path
9. Autopilot guides proteins in brain
10. New method for detection of phosphoproteins reveals regulator of melanoma invasion
11. New high-throughput screening technique makes probing puzzling proteins possible
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/5/2016)... Dec. 5, 2016  The Office of Justice ... "Can CT Scans Enhance or Replace Medico Legal ... of supporting or replacing forensic autopsies with postmortem ... In response to recommendations made by ... using CT scans as a potential component of ...
(Date:11/30/2016)...  higi SH llc (higi) announced today the ... brands, industry thought-leaders and celebrity influencers looking to ... taking steps to live healthier, more active lives. ... has built the largest self-screening health station network ... who have conducted over 185 million biometric screenings.  ...
(Date:11/28/2016)... 2016 "The biometric system ... The biometric system market is in the growth ... near future. The biometric system market is expected to ... a CAGR of 16.79% between 2016 and 2022. Government ... technology in smartphones, rising use of biometric technology in ...
Breaking Biology News(10 mins):
(Date:12/7/2016)... 7, 2016  Genprex, Inc. a biopharmaceutical company ... treatments, today announced that it has retained ICR ... strategic communications and advisory firm, to develop and ... will combine investor relations, public relations and digital ... profile of Genprex and its lead candidate Oncoprex, ...
(Date:12/7/2016)... DIEGO , December 7, 2016 ... in the International Journal of Molecular Sciences a team of ... 1 ] have demonstrated that expression of NR2F6 ...  These scientists tested for NR2F6 in patient,s cervical cancer tissue ... their tumors. "This is an interesting study and ...
(Date:12/7/2016)... ... December 07, 2016 , ... JULABO USA is ... cart. The new website has been designed to provide the best user-friendly experience ... to access detailed product information, read educational industry content as well as share ...
(Date:12/6/2016)... , Dec. 6, 2016 The American Botanical ... adoption of arnica ( Arnica montana ) through ... ABC,s HerbMedPro database, a comprehensive, interactive ... and clinical research data on the uses and ... Naturopathica, a wellness company with healing ...
Breaking Biology Technology: