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:2/16/2017)... , Feb. 16, 2017  Genos, a community ... that it has received Laboratory Accreditation from the ... is presented to laboratories that meet stringent requirements ... scientifically rigorous processes. "Genos is committed ... laboratory practices. We,re honored to be receiving CAP ...
(Date:2/9/2017)... Feb. 9, 2017 The biomass boiler market ... the biomass boiler market globally in terms of revenue ... boilers. The market for biomass boilers has been segmented ... application, and country/region. The market based on feedstock type, ... residues, biogas & energy crops, urban residues, and others. ...
(Date:2/8/2017)... Report Highlights The global biosurgery ... billion in 2016 at a compound annual growth rate ... Includes - An overview of the global market for ... from 2015 and 2016, and projections of compound annual ... market on the basis of product type, source, application, ...
Breaking Biology News(10 mins):
(Date:2/27/2017)... ... February 27, 2017 , ... In starting a program to hire ... grandfather, “Hire for attitude. Train for skill.” , In keeping with this philosophy, the ... as a salesman. Zamzow is hoping to replicate the practice throughout the company. , ...
(Date:2/24/2017)... SAN FRANCISCO, CA (PRWEB) , ... February 24, 2017 , ... ... awarding of a $224K grant from the National Institute of Mental Health (NIMH) for ... is based on Delpor’s PROZOR technology and is expected to deliver therapeutic ...
(Date:2/24/2017)... , Feb. 24, 2017  Driven by consumers, ... are now the fastest growing categories, finds the ... Actives in Personal Care: Multi-regional Market Analysis and ... management consulting firm Kline. "Biotechnology actives ... make them more effective for skin and hair ...
(Date:2/24/2017)... 24, 2017  OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), ... a Key Opinion Leader event to highlight new clinical ... poster presentation at the upcoming 2017 ASCO-SITC Immuno-Oncology Symposium ... will be held in-person and via live webcast on ... AM PST at the Lotte New York Palace Hotel ...
Breaking Biology Technology: