An Australian-led research team has obtained the world’s first 3D pictures of insulin in the process of binding to cell surfaces so that the cells can take up sugar from the blood. The work will enable development of improved forms of insulin for treating type 1 and type 2 diabetes.
The insulin binding process, in which the insulin docks with a specialised insulin receptor on the surface of the cells, has been under investigation for more than 20 years. If the docking process doesn’t work for some reason, cells can’t take up sugar from the blood and convert it into energy.
Researchers from the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne used x-ray diffraction at the Australian Synchrotron to obtain highly detailed, three-dimensional images of insulin and the insulin receptor. The synchrotron x-ray images show that both insulin and the insulin receptor change their shape in order to bind with each other.
The work is described in a paper published today in Nature, one of the world’s most prestigious scientific journals.
WEHI Associate Professor Mike Lawrence said the work would not have been possible without access to the Australian Synchrotron’s specialised MX2 micro-focus beamline and the synchrotron MX team led by Dr Tom Caradoc-Davies, who keep the beamline operating at world-class standard.
The micro-focus beamline has a highly-focused x-ray beam that allows scientists to collect useful diffraction data from very small crystals such as those used in the insulin work, which were comparable to the width of a human hair. A further advantage is that the synchrotron x-ray beam is thousands of times brighter than laboratory x-ray sources, enabling experiments to be completed in minutes rather than weeks.
“What made the insulin work possible for us was being able to make regular visits to a local synchrotron instead of having to travel overseas,” Mike Lawrence said. “It’s difficult to grow crystals of insulin docking with its receptor, but frequent synchrotron visits meant we could optimise the crystal preparation methods and the experimental settings rather than guessing what might work.”
In addition to the Melbourne-based WEHI researchers, who included Dr Colin Ward and Dr John Menting, the research team involved collaborators from the US, UK and the Czech Republic.
The synchrotron x-ray pictures could pave the way for improved types of insulin that can be takenless frequently, or given in ways other than by injection, or don’t require refrigerated storage.
ENDS
Contact:
Andrew Peele, Australian Synchrotron – 0408 388 467