Scripps study may help advance drug-design biotechnology
The structural details demonstrate how certain proteins can interact with two separate signals to create a single integrated output. This could give researchers an important advantage in fine-tuning various signals sent among partnered proteins, impacting the drug’s overall course of action.
“Thyroid, vitamin D and retinoid receptors all rely on integrated signals — their own signal plus a partner receptor,” TSRI associate professor Kendall Nettles, who led the study with TSRI associate professor Douglas Kojetin, said. “These new findings will have important implications for drug design by clearly defining exactly how these signals become integrated, so we will be able to predict how changes in a drug’s design could affect signaling.”
The researchers used several complementary technologies, such as hydrogen/deuterium exchange (HDX), mass spectrometry, X-ray crystallography and nuclear magnetic resonance (NMR). This helped scientists find the mechanism that integrated the two signaling pathways.
“Nuclear receptors bind different types of molecules, and some of these receptors physically interact with each other to integrate different signals,” Kojetin said. “Earlier studies basically accepted this without any structural evidence for communication between receptors. This is the first time that anyone has looked at what’s actually going on at the atomic level.”
Results from the study were published recently in the journal Nature Communications.