When blood glucose levels are high, a segment within insulin undergoes a hinge-like rotation to expose otherwise hidden surfaces that subsequently engage the insulin receptor, reports a team led by Australian researchers (Menting JG et al. Proc Natl Acad Sci U S A. 2014;111:E3395-E3404). The findings were made through diverse biological, biochemical, crystallographic, and spectroscopic experiments.
When the investigators restrained the hinge within insulin so that the closed form was preserved, receptor binding was blocked. This form likely evolved to permit insulin’s efficient production and safe storage within the pancreas, the authors noted. A form engineered to remain open maintained activity, but with a trade-off of protein instability.
Hampton T. Mystery of Insulin Binding Revealed. JAMA. 2014;312(13):1291. doi:10.1001/jama.2014.13443