There may be a sort of main power switch that could be tripped suggests a three-dimensional image of one of the proteins.

"It's important to understand how this extraordinary family of receptors work," said co-author Robert J. Lefkowitz, M.D., James B. Duke Professor of Medicine and Howard Hughes Medical Institute Investigator. "This is the kind of finding that answers a basic curiosity, but can also be of benefit if we can develop new drugs or improve the ones we have."
The research marks a collaborative reunion between Lefkowitz and Brian K. Kobilka, M.D., chair of molecular and cellular physiology at Stanford University School of Medicine. The two researchers – friends who first collaborated when Kobilka was a trainee in Lefkowitz's laboratory at Duke - shared the 2012 Nobel Prize in Chemistry for their discoveries involving the G-protein coupled receptors (GPCRs), which are activated by signaling proteins to detect hormones, neurotransmitters, pain, light.
In the current work, the researchers used X-ray crystallography to develop an atom-scale image of one of the principal signaling molecules that regulate GPCRs. This protein is called beta-arrestin1, which, among other things, works to dim a cell's response to hormones such as adrenalin.
The researchers were able to isolate and capture the beta-arrestin1 protein in an active state as it binds to a segment of the GPCR – a first. That snapshot, in high resolution, revealed that the structural conformation or shape of the protein in its active state is strikingly different than when it is inactive.
Such changes suggest there may be a general molecular mechanism that activates the beta-arrestin1 – a sort of main switch that controls the multi-functional signaling proteins.
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The researchers are now pursuing additional structural imaging of the signaling complex consisting of beta-arrestin1 and the entire receptor protein.
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