Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists at Scripps Research Institute discover how 2 proteins help keep cells healthy

03.12.2012
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."

In addition to Otomo, authors of the paper, "Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy," include Chinatsu Otomo and Zoltan Metlagel of TSRI, and Giichi Takaesu of Keio University in Tokyo, Japan.

This research was supported by National Institutes of Health (NIH) grant GM092740 and by funds from Japan Science and Technology Agency through the Keio Kanrinmaru Project.

Mika Ono | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht Cloud Formation: How Feldspar Acts as Ice Nucleus
09.12.2016 | Karlsruher Institut für Technologie

nachricht Closing the carbon loop
08.12.2016 | University of Pittsburgh

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>