Ancient protein flexibility may drive 'new' functions

A mechanism by which stress hormones inhibit the immune system, which appeared to be relatively new in evolution, may actually be hundreds of millions of years old.

A protein called the glucocorticoid receptor or GR, which responds to the stress hormone cortisol, can take on two different forms to bind DNA: one for activating gene activity, and one for repressing it. In a paper published Dec. 28 in PNAS, scientists show how evolutionary fine-tuning has obscured the origin of GR’s ability to adopt different shapes.

“What this highlights is how proteins that end up evolving new functions had those capacities, because of their flexibility, at the beginning of their evolutionary history,” says lead author Eric Ortlund, PhD, associate professor of biochemistry at Emory University School of Medicine. Dr. Ortlund is also a faculty member in the BCDB and MSP programs.

GR is part of a family of steroid receptor proteins that control cells’ responses to hormones such as estrogen, testosterone and aldosterone. Our genomes contain separate genes encoding each one. Scientists think that this family evolved by gene duplication, branch by branch, from a single ancestor present in primitive vertebrates.

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