Structural delineation of the calcineurin-NFAT interaction and its parallels to PP1 targeting interactions.
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.
Li
Huiming
H
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Rao
Anjana
A
Hogan
Patrick G
PG
D000595:Amino Acid Sequence; D001665:Binding Sites; D019703:Calcineurin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003198:Computer Simulation; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D025941:Protein Interaction Mapping; D054645:Protein Phosphatase 1; D017386:Sequence Homology, Amino Acid; D013912:Threonine / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments; D010750:Phosphoproteins; D014157:Transcription Factors; D013912:Threonine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1