Abstract
Calcineurin is a phosphoprotein phosphatase that channels intracellular Ca signals into multiple biological pathways. Calcineurin is known to interact directly with its substrate nuclear factor of activated T cells (NFAT or NFATc), with other substrates, and with several targeting and scaffold proteins including AKAP79 and Cabin1/cain. The calcineurin-NFAT interaction depends on recognition of a PxIxIT sequence motif present in NFAT-family proteins and in certain other calcineurin-interacting proteins. Here, we define the structural basis for the interaction of calcineurin with NFAT and with other proteins possessing the PxIxIT motif. The calcineurin-PxIxIT contact has a direct parallel in the contact of protein phosphatase 1 with its regulatory proteins, suggesting that the evolution of these related phosphatases involved local remodelling of an ancestral docking site.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Calcineurin / chemistry*
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Calcineurin / genetics
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Calcineurin / metabolism*
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Computer Simulation
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Cross-Linking Reagents
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / metabolism*
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Humans
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Molecular Sequence Data
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NFATC Transcription Factors
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Nuclear Proteins*
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Phosphoprotein Phosphatases / metabolism*
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Phosphoproteins / chemistry
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Binding
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Protein Conformation
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Protein Folding
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Protein Interaction Mapping
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Protein Phosphatase 1
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Sequence Homology, Amino Acid
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Threonine / chemistry
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Threonine / genetics
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Transcription Factors / chemistry*
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Transcription Factors / metabolism*
Substances
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Cross-Linking Reagents
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DNA-Binding Proteins
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NFATC Transcription Factors
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Nuclear Proteins
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Peptide Fragments
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Phosphoproteins
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Transcription Factors
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Threonine
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Calcineurin
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Phosphoprotein Phosphatases
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Protein Phosphatase 1