Corporate Banner
Satellite Banner
Crystallography
Scientific Community
 
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
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 2,500+ scientific posters on ePosters
  • More than 3,700+ 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

TSRI Scientists Find Clues to Cancer Drug Failure
A pair of studies show how the primary protein responsible for multidrug chemotherapy resistance changes shape.
Thursday, March 05, 2015
Scientists Solve 40-year Mystery of How Sodium Controls Opioid Brain Signaling
The findings pave way for new therapies for treating pain and mood disorders.
Thursday, January 16, 2014
Team Reveals Key Protein Interactions Involved in Neurodegenerative Disease
New study reveals the structure of c-jun-N-terminal kinases (JNK) enzymes.
Thursday, November 15, 2012
Scientists Find Structure of a Protein that Makes Cancer Cells Resistant to Chemotherapy
A research team at the Scripps Research Institute has obtained the first glimpse of a protein that keeps certain substances, including many drugs, out of cells.
Monday, March 30, 2009
Scientific News
Structural Discoveries Could Aid in Better Drug Design
Scientists have uncovered the structural details of how some proteins interact to turn two different signals into a single integrated output.
New Mathematics Advances the Frontier of Macromolecular Imaging
Berkeley Lab’s M-TIP solves the reconstruction problem for fluctuation X-ray scattering.
Diamond Helps Develop New Way of Studying the Tiniest Microcrystals
Researchers have developed a new type of sample holder for ‘serial protein crystallography’.
Crystal Clear Images Uncover Secrets of Hormone Receptors
NIH researchers gain better understanding of how neuropeptide hormones trigger chemical reactions in cells.
TOPLESS Plants Provide Clues to Human Molecular Interactions
Scientists at Van Andel Research Institute have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer.
Advancing Cancer Drug Design with Image of Key Protein
Scientists have pioneered the use of a high-powered imaging technique to picture in exquisite detail one of the central proteins of life – a cellular recycling unit with a role in many diseases.
Mould Unlocks New Route to Biofuels
Scientists at The University of Manchester have made an important discovery that forms the basis for the development of new applications in biofuels and the sustainable manufacturing of chemicals.
'Invisible' Protein Structure Explains the Power of Enzymes
A research group at Umeå University in Sweden has managed to capture and describe a protein structure that, until now, has been impossible to study.
Unraveling the Elusive Structure of HIV Protein
Snapshots of HIV virus’ proteins may help design new ways to fight the disease.
Blueprinting Cell Membrane Proteins
Recent breakthrough will make the blueprinting process faster, easier and cheaper, and should have major implications in the field of drug discovery and development.
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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!