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.