African swine fever virus protein A238L interacts with the cellular phosphatase calcineurin via a binding domain similar to that of NFAT.
The African swine fever virus protein A238L inhibits activation of NFAT transcription factor by binding calcineurin and inhibiting its phosphatase activity. NFAT controls the expression of many immunomodulatory proteins. Here we describe a 14-amino-acid region of A238L that is needed and sufficient for binding to calcineurin. By introducing mutations within this region, we have identified a motif (PxIxITxC/S) required for A238L binding to calcineurin; a similar motif is found in NFAT proteins. Peptides corresponding to this domain of A238L bind calcineurin but do not inhibit its phosphatase activity. Binding of A238L to calcineurin stabilizes the A238L protein in cells. Although A238L-mediated suppression of NF-kappaB-dependent gene expression occurs by a different mechanism, the A238L-calcineurin interaction may be required to stabilize A238L.
Miskin
J E
JE
Institute for Animal Health, Pirbright Laboratory, Pirbright, Surrey GU24 0NF, United Kingdom.
Abrams
C C
CC
Dixon
L K
LK
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019703:Calcineurin / Q000378:metabolism*; D020134:Catalytic Domain; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000378:metabolism; D013552:Swine; D014157:Transcription Factors / Q000378:metabolism*; D014709:Vero Cells; D014764:Viral Proteins / Q000378:metabolism
C113585:A238L protein, African swine fever virus; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments; D014157:Transcription Factors; D014764:Viral Proteins; D019703:Calcineurin