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Study offers new understanding of cell signaling networks tied to diabetes and cancer

March 19, 2017

The project involved an ongoing collaboration between Cheng's research group at UTMB, experts in the study of cAMP signaling, and UCSD professor of medicine Virgil Woods Jr. and colleagues at UCSD, pioneers in the development and application of hydrogen/deuterium exchange mass spectrometry (DXMS) technology. Compared with other protein-analysis techniques, DXMS is especially good at studying the structural motion of proteins.

Using this novel approach, the investigators were able to reveal, in fine detail, that cAMP interacts with its two known binding sites on Epac2 in a sequential fashion and that binding of cAMP changes the shape of the protein in a very specific way - switching on its activity by exposing further signaling interaction sites on Epac2.

"DXMS analysis has proved to be an amazingly powerful approach, alone or in combination with other techniques, in figuring out how proteins work as molecular machines, changing their shapes - or morphing - in the normal course of their function," said Woods. "This will be of great use in the identification and development of therapeutic drugs that target these protein motions."

Source: University of Texas Medical Branch at Galveston