G protein-coupled receptors (GPCRs) constitute a large protein family of receptors that are able to sense molecules outside of the cell, such as light, odorants, and hormones. These extracellular cues then trigger a cascade of events that leads to physiological changes in the cell. However, these activated receptors are soon "turned off" in order to allow cells to adapt to changes in their environment and avoid oxidative damage.

This process, called desensitization, is initiated by a family of proteins known as GPCR kinases (GRKs). Defects in desensitization are known to cause night blindness, and abnormally elevated GRK activity is believed to play a role in heart failure and addiction.
 
Previously, scientists suspected that GRKs have a "receptor docking site" responsible for recognition of activated GPCRs, but the molecular architecture of this docking site and how it serves as a trigger for activation of kinase activity was not known.
 
In a paper recently published in The EMBO Journal, Life Sciences Institute Research Associate Professor John Tesmer and colleagues describe the crystal structure of GRK6 in a novel, closed conformation, in which all the regions known to be critical for receptor phosphorylation (the addition of a phosphate group to a protein group) are ordered and have coalesced to form a likely docking site for activated receptors. This is the most complete GRK structure determined to date.

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