Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Scientists Discover How Two Proteins Help Keep Cells Healthy

Published: Thursday, December 06, 2012
Last Updated: Thursday, December 06, 2012
Bookmark and Share
The work has implications for cancer drug development.

Scientists at The Scripps Research Institute (TSRI) have determined how two proteins help create organelles, or specialized subunits within a cell, that play a vital role in maintaining cell health. This discovery opens the door for research on substances that could interfere with the formation of these organelles and lead to new therapies for cancer.

The study, published online ahead of print on December 2, 2012, by the journal Nature Structural & Molecular Biology, focuses on the structure and function of the two proteins, ATG12 and ATG5. These proteins need to bond correctly to form an organelle called the autophagosome, which acts like a trash bag that removes toxic materials and provides the cell with nutrition through recycling.

“Our study focuses on one of the big mysteries in our field,” said Takanori Otomo, the TSRI scientist who led the effort. “These proteins are linked, but no one has explained why clearly. We’re very excited to have determined the structure of these linked proteins so that the information is available to do the next level of research.”

Asking Questions, Finding Answers

At the beginning of the study, Otomo and colleagues knew that many proteins work together to form autophagosomes as part of the process known as autophagy, which breaks down large proteins, invasive pathogens, cell waste, and toxic materials. As part of this process, one key protein, LC3, attaches to a lipid, or fat molecule, on the autophagosome membrane. Yet LC3 cannot attach to a lipid without the help of ATG12 and ATG5, and a cell will only form an autophagosome if the linkage, or conjugate, between these two molecules has been established.

Otomo and colleagues set out to determine the shape of the ATG12-ATG5 conjugate, and to find out why it was needed for LC3 lipidation.

Using a method called X-ray crystallography, the scientists were able to unveil the details of this conjugate. When ATG12 and ATG5 come together, they form a rigid architecture and create a surface area that is made up of evolutionarily conserved amino acids and facilitates LC3 lipidation. The researchers confirmed this finding by mutating those conserved amino acids , which prevented an autophagosome from forming.

Otomo and colleagues also identified a surface on the ATG12-ATG5 conjugate that binds to ATG3, another enzyme required to attach LC3 to the lipid.

Toward Better Understanding and New Cancer Treatments

With this new knowledge, the researchers hope to design molecules that inhibit autophagosome formation, a direction of research that has implications for cancer treatment. A drug that directly inhibits ATG3 binding, for example, could be used in coordination with current therapies to make cancer treatments more effective, preventing a cancer cell from recycling nutrients and prolonging its survival.

“Ultimately, we’d like to understand the molecular mechanisms of each step of autophagy,” he said, “As we make progress toward this goal, we will have a better idea of how to manipulate the pathway for therapeutic purposes. This field is still young and there are a lot of unknowns. This work is just the beginning.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More Than 5,000+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Pinpointing Ebola’s Weak Spots
New study illuminates structure of mystery protein.
Thursday, August 11, 2016
TSRI Awarded $20M for Precision Medicine Initiative Cohort Program
NIH announces the first instalment of a $120M grant has been awarded to The Scripps Research Institute for its role in a national precision medicine initiative.
Monday, July 11, 2016
New Cancer Drug Target in Dual-Function Protein
Scientists at The Scripps Research Institute (TSRI) have identified a protein that launches cancer growth and appears to contribute to higher mortality in breast cancer patients.
Wednesday, June 29, 2016
Memory Suppressor Gene Identified
Scientists have identified a unique memory suppressor gene in the brain cells of Drosophila, the common fruit fly, a widely recognized substitute for human memory studies.
Tuesday, April 19, 2016
Promising Results for AIDS Vaccine
Engineered vaccine protein binds key immune cells that exist in nearly everyone.
Wednesday, March 30, 2016
New Targets for Diabetes, Inflammation Discovered
The Scripps Research Institute and Salk Scientists discover 'outlier' enzymes that could offer new targets to treat diabetes and inflammation.
Tuesday, March 29, 2016
Versatile New Molecule-Building Technique
Chemists at The Scripps Research Institute (TSRI) have devised a new and widely applicable technique for building potential drug molecules and other organic compounds.
Tuesday, January 19, 2016
Flipping Molecular 'Switch' May Reduce Nicotine's Effects in the Brain
Scientists at The Scripps Research Institute (TSRI) have discovered that a lipid (fat molecule) in brain cells may act as a “switch” to increase or decrease the motivation to consume nicotine.
Friday, January 15, 2016
TSRI Team Comes Together with Rare Disease Community
Don’t worry, science fiction fans, the machines aren’t taking over quite yet. It turns out humans still beat computers at reading and comprehending text.
Monday, January 11, 2016
Single ‘Transformer’ Proteins
A new study led by scientists at The Scripps Research Institute (TSRI) and St. Jude Children’s Research Hospital shows how a protein involved in cancer twists and morphs into different structures.
Monday, January 11, 2016
Pushing Drug Discovery Forward
A new study, led by scientists at The Scripps Research Institute (TSRI), shows how different pharmaceutical drugs hit either the “on” or “off” switch of a signaling protein linked to asthma, obesity and type 2 diabetes.
Monday, December 14, 2015
TSRI Team Finds Unique Anti-Diabetes Compound
Scientists from The Scripps Research Institute (TSRI) have deployed a powerful new drug discovery technique to identify an anti-diabetes compound with a novel mechanism of action.
Thursday, December 10, 2015
Protein 'Talks' to Wrong Partners in Cystic Fibrosis
Scientists at The Scripps Research Institute (TSRI) have found evidence that a mutant protein responsible for most cases of cystic fibrosis is so busy “talking” to the wrong cellular neighbors that it cannot function normally and is prematurely degraded.
Monday, December 07, 2015
'Fingerprints' for Major Drug Development Targets
For the first time, scientists from the Florida campus of The Scripps Research Institute (TSRI) have created detailed “fingerprints” of a class of surface receptors that have proven highly useful for drug development.
Friday, December 04, 2015
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
Thursday, November 26, 2015
Scientific News
Mass Spec Technology Drives Innovation Across the Biopharma Workflow
With greater resolving power, analytical speed, and accuracy, new mass spectrometry technology and techniques are infiltrating the biopharmaceuticals workflow.
One Step Closer to Precision Medicine for Chronic Lung Disease Sufferers
A study led by University of North Carolina at Chapel Hill, and National Jewish Health, has provided evidence of links between SNPs and known COPD blood protein biomarkers.
Atmosphere Acidity Minimised to Preindustrial Levels
Sheet ice study shows acidic pollution of the atmosphere has now almost returned to preindustrial levels.
A Diversity of Genomes
New DNA from understudied groups reveals modern genetic variation, ancient population shifts.
“Sixth Sense” May Be More Than Just A Feeling
The NIH Study shows that two young patients with a mutation in the PIEZ02 have problems with touch and proprioception, or body awareness.
Gene Could Reduce Female Mosquitoes
Virginia Tech researchers have found a gene that can reduce female mosquitoes over many generations.
Biomolecular Manufacturing ‘On-the-Go’
Wyss Institute team unveils a low-cost, portable method to manufacture biomolecules for a wide range of vaccines, other therapies as well as diagnostics.
Improving Crop Efficiency with CRISPR
New study of CRISPR-Cas9 technology from Virginia Tech shows potential to improve crop efficiency.
Fighting Cancer with Sticky Nanoparticles
Treatment that uses bioadhesive nanoparticles drug carriers proved more effective than conventional treatments for certain cancers.
Stem Cell ‘Heart Patch’ Almost Perfected
Scientists aiming to perfect and test 3D "heart patches" in animal model, last hurdle before human patients.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!