Synchrotron sheds light on damage control protein

New Zealand and Australian researchers have collaborated in investigating the protein Apoptosis signal-regulating kinase 1 (ASK1), which plays an important role in controlling how a cell responds to damage. Their study results have been published in the journal Proceedings of the National Academy of Sciences.

According to Dr Peter Mace, from the University of Otago, ASK1 can push a cell towards a process of programmed cell death for the good of the body, if damage to a cell is too great. The protein gets its name from an Ancient Greek word meaning ‘falling off’ (apoptosis) and is used to describe the process of the body actively programming cells to die, rather than losing them via injury.

Using the Australian Synchrotron, Dr Mace and his fellow researchers used crystallography studies to determine ASK1’s molecular structure. They also performed other biochemical experiments to better understand the protein.

“Using the synchrotron’s MX Beamlines, we collected data from difficult samples to help solve questions the research team had about the structure of the protein,” said Dr Tom Caradoc-Davies, a principal scientist at the Australian Synchrotron, who claims these questions may not have been solved for many years were it not for the team’s regular access to the synchrotron.

The researchers found that ASK1 has unexpected parts to its structure that help control how the protein is turned on, and that an entire family of ASK kinases share these features. This is important, said Dr Mace, “because in diseases such as Parkinson’s, stomach cancer and melanoma, there can be either too much or too little ASK1 activity”.

Dr Mace said the findings add to our understanding of how cells can trigger specific responses to different threats or damage encountered, such as oxidants, which damage the body’s tissues by causing inflammation. He added that kinases are excellent targets for developing new drugs because they have a ‘pocket’ in their structure that such compounds can bind to. To develop better drugs, he said, we need to understand more about how they are controlled — this is the goal of several projects in his lab.