Neutrophils are a type of white blood cell that are part of our innate immune system. Their activities require tight regulation to avoid unwanted inflammation and autoimmune diseases. Here we show that the protein GPR97, which is found on the surface of neutrophils, plays a role in this process. It associates with a potent proteolytic protein found on neutrophils, the membrane proteinase 3 (mPR3). Together with other protein interaction partners we identified such as PAR2, this association is a key step leading to neutrophil activation. Structural/functional analysis of the GPR97 extracellular region identified two mPR3-binding domains. Both GPR97 and mPR3 are upregulated on the surface of disease-associated neutrophils, suggesting a role in pathologic inflammation.
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