How receptors take shape
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An international collaboration has determined the activated crystal structure of the human glucagon receptor — which plays a critical role in regulating blood sugar levels — in a complex with a partial activator.
The team, which includes ShanghaiTech University researchers, had previously reported glucagon receptor’s inactive structure. They have now compared the receptor’s inactive and active structures and discovered stark differences in shape, or conformation. This provides useful insights into the mechanics of molecule binding and activation. Two extracellular receptor segments, known as the stalk region and first extracellular loop, were found to play essential roles in recognizing glucagon, glucagon receptor’s natural physiological activator.
This discovery is set to benefit our understanding of G-protein coupled receptors, an important category of biological receptors to which glucagon receptor belongs.
- Nature 553, 106−110 (2018). doi: 10.1038/nature25153