Australasian Science: Australia's authority on science since 1938

A Diabetes Treatment from Snail Venom

The 3D structure of an insulin found in cone snail venom has revealed how these highly efficient natural proteins can operate faster than human insulin.

The research, conducted using the Australian Synchrotron, discovered that the Con-Ins G1 protein was able to bind to human insulin receptors, signifying the potential for its translation into a human therapeutic agent.

“We found that cone snail venom insulins work faster than human insulins by avoiding the structural changes that human insulins undergo in order to function – they are essentially primed and ready to bind to their receptors,” said A/Prof Mike Lawrence of The Walter and Eliza Hall Institute of Medical Research, who led the international collaboration.

Lawrence described human insulins as “clunky” by comparison. “The structure of human insulins contain an extra ‘hinge’ component that has to open before any ‘molecular handshake’ or connection between insulin and receptor can take place,” he explained.

“By studying the three-dimensional structure of this snail venom insulin, we’ve found how to dispense with this ‘hinge’ entirely, which may accelerate the cell signalling process and thus the speed with which the insulin takes effect.”

Published in Nature Structural and Molecular Biology, the findings build on the 2015 discovery that the marine cone snail Conus geographus used an insulin-based venom to trap its prey. Unsuspecting fish prey would swim into the invisible trap and immediately become immobilised in a state of hypoglycaemic shock induced by the venom.

“Our Flinders University colleagues have shown that the cone snail insulin can switch on human insulin cell signalling pathways, meaning the cone snail insulin is able to successfully bind to human receptors,” said co-author Dr Helena Safavi-Hemami of The University of Utah. “The next step in our research, which is already underway, is to apply these findings to the design of new and better treatments for diabetes, giving patients access to faster-acting insulins,” she said.