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A new route to G proteins
October 2019
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SAN DIEGO—G-protein coupled receptors are a popular drug target, and the current theory is that G proteins are exclusively activated by GPCRs. But recent research out of UC San Diego found another method. Using high-resolution X-ray crystallography, they saw GPCR-independent activation of a heterotrimeric G protein by a member of the guanine-nucleotide exchange modulator (GEM) family. Despite the fact that they bind on different sites on G proteins, GPCRs and GEMs share part of the pathway that results in nucleotide exchange and activation.
 
“Given the central and critical role that heterotrimeric G proteins play in health and disease, and attention that they have been attracting from the broad scientific audience over many decades, this is a major advance in our understanding of G proteins,” said co-author Dr. Pradipta Ghosh, professor and founding director of the Center for Network Medicine at UC San Diego School of Medicine.

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