Alzheimer’s - How protein structure affects disease

Proteins are the body's most essential building blocks. They are also the cell’s molecular engines, controlling all of the body’s functions. Their actions are diverse and complex and are dictated by their precise three-dimensional (3D) structure.

Professor Michael Parker, head of SVI’s Structural Biology Unit, is one of Australia’s leading structural biologists. More than 100 three-dimensional atomic structures of proteins involved in major diseases have been solved in his Unit. The Unit provides early stage drug discovery tools to aid researchers translate their basic discoveries into drugs.

Michael explains the importance of determining protein structure, “These structures allow us to ‘see’ biological processes at their most fundamental level: through knowledge of the 3D structure, we can identify which proteins interact, and how they do so, how drugs act, and how certain diseases proceed at an atomic level.”

He goes on to explain that more recently, 3D structures have been used to design ‘smart drugs’. This approach, which uses knowledge of the structure of a protein to custom-design drugs to interact with it, has the potential to shave years and millions of dollars off the traditional drug-design approaches.

Studies carried out by researchers in the Unit have contributed to the identification of targets for cancer therapy, and to a greater understanding of the mechanisms of cancer growth and spread. Particular focus is on a protein complex called the GM-CSF/IL-3/IL-5 receptor, a cell signalling receptor in the blood control system. Malfunctions in the signalling pathway result in diseases such as certain types of leukaemia. Their discovery helps to explain, for the first time, how this receptor is activated and will form the springboard for the development of new treatments.

Other areas of interest for researchers in the Unit include neurobiology (in collaboration with scientists at the Florey Neurosciences Institute and Melbourne University) and infection, aimed at determining how infectious organisms such as bacteria and viruses exert their detrimental effects.

Much of our knowledge of disease has come from an improved understanding of the function of proteins. This knowledge gives us the best possibility of designing new drugs and treatment strategies.