Key result
A 14-amino-acid region in viral protein A238L drives calcineurin binding to stabilize the protein.
The African swine fever virus protein A238L binds to calcineurin via a motif similar to NFAT, which stabilizes the viral protein.
Animal data preclude clinical translation; leaves open whether this motif drives ASFV virulence in vivo.
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.
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Miskin et al. (2000) studied this question. A238L protein mutations was evaluated on Binding to calcineurin and inhibition of phosphatase activity. A 14-amino-acid region of the African swine fever virus protein A238L containing a PxIxITxC/S motif is required and sufficient for binding to calcineurin, which stabilizes the A238L protein.
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