The first 3D image of a key protein known to be involved in the development of blood and other cancers has been created by researchers at the Walter and Eliza Hall Institute (WEHI) in Melbourne.
The image of the Trib1 protein, a protein that regulates how and when other proteins are degraded, can be used to develop new drugs to treat cancers such as leukaemia.
Dr James Murphy and Dr Isabelle Lucet from WEHI, in collaboration with Dr Peter Mace from the University of Otago, New Zealand, characterised the protein at the Australian Synchrotron.
“The structure of Trib1 is really exciting,” Dr Murphy said. “We can now see how Trib1 is able to trigger protein destruction, which will provide critical clues for developing drugs that target Trib1 to treat cancers.”
Image of the Trib1 protein. Courtesy of Dr James Murphy, Walter and Eliza Hall Institute.
Dr Murphy said that Trib1 was an unusual type of protein called a pseudokinase, which were once thought to be evolutionary dead ends. Visualising the protein enabled the team to conclude that Trib1 acted as a scaffold to bring many proteins together by forming a large complex that caused specific proteins to be degraded.
Excess proteins can drive the abnormal production of immune cells, causing a type of blood cancer called acute myeloid leukemia (AML). Dr Mace said some AML patients have too much Trib1, which causes a loss of proteins that would normally inhibit cancer.
“As well as explaining how Trib1 functions, our research could help us design novel therapeutic agents for the treatment of AML,” Dr Mace said.
Australian Cancer Research Foundation together with the Health Research Council of New Zealand, the New Zealand government, the Australian National Health and Medical Research Council and the Victorian Government Operational Infrastructure Support Program have supported this research.
Image of Dr James Murphy and Dr Isabelle Lucet courtesy of Walter and Eliza Hall Institute