Scientists have finally pieced together the structure of the insulin receptor in human cells, paving the way for advancements in diabetes and cancer treatment.
Structural biologist, Associate Professor Michael Lawrence of the Walter and Eliza Hall Institute of Medical Research and colleagues report their findings this week in the Proceedings of the National Academy of Sciences.
When insulin binds to receptors on cells in the human body, it triggers a chain of events that result in glucose uptake from the blood.
"We're interested in how all this happens at the molecular level," says Lawrence.
In 2006, Lawrence and colleagues used protein crystallography to image the insulin receptor protein.
They identified one of the two elements that make up the initial binding site for insulin (light blue strands in the image) but the second element eluded them.
"The work at that time was an enormous advance, but there was still a missing piece that we were unable to find," says Lawrence.
Most recently they have discovered that second element (pink helix in the image).
"Insulin cannot bind either piece by itself, it requires the two pieces to be together as shown in order for any binding to the receptor to occur," says Lawrence.
After insulin has bound these two pieces, there are further (yet-to-be-elucidated) interactions with the remainder of the receptor, before glucose uptake can be effected.
Lawrence says the findings are important for researchers who are trying to develop insulin substitutes that can be taken orally, instead of injected.
He says it also might help in the development of insulin substitutes that are longer-lasting or quicker acting, reducing the number of times people with diabetes need to top up their insulin, or how quickly they need to respond to low blood sugar.
Lawrence says the findings could also help in the development of anti-cancer drugs.
He says the insulin receptor system is very similar to another receptor system - called the Type 1 Insulin-like Growth Factor Receptor (IGF-1R), which is involved in abnormal cell growth in cancer.
"Anything you learn from the one system immediately carries over to the other," says Lawrence.
"In a sense we've learnt about two systems even though we're working with one."
Lawrence says it is possible to design molecules that would bind to the IGF-1R system and block its functioning.
He says there are a number of companies targeting the IGF-1R system in the development of anti-cancer drugs.
Lawrence says the main remaining piece of the puzzle is how the insulin 'key' fits in its receptor 'lock'.
"That's what we're working on at the moment," he says.