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The structure of the RCAN1:CN complex explains the inhibition of and substrate recruitment by calcineurin
2020
Science Advances
Regulator of calcineurin 1 (RCAN1) is an endogenous inhibitor of the Ser/Thr phosphatase calcineurin (CN). It has been shown that excessive inhibition of CN is a critical factor for Down syndrome and Alzheimer's disease. Here, we determined RCAN1's mode of action. Using a combination of structural, biophysical, and biochemical studies, we show that RCAN1 inhibits CN via multiple routes: first, by blocking essential substrate recruitment sites and, second, by blocking the CN active site using
doi:10.1126/sciadv.aba3681
pmid:32936779
pmcid:PMC7458460
fatcat:rfwib2vwrjabxbpmi6mhb46lza