Alphaherpesvirus pUL21 homologs use non-canonical sequences to compete with cellular adaptors for protein phosphatase 1 binding.

ABSTRACT: Protein phosphatase 1 (PP1) is a key regulator of cellular phosphorylation and its activity is regulated via binding to cellular regulatory proteins via conserved short linear motifs (SLiMs). The herpes simplex virus (HSV)-1 protein pUL21 binds PP1 via the TROPPO motif, which lacks sequence similarity to canonical PP1-binding SLiMs. Here, we combine structure prediction, mutagenesis, and biophysical assays to elucidate the molecular basis of this interaction. AlphaFold2-Multimer structural models suggest that the TROPPO motifs of pUL21 and of pORF38, the varicella-zoster virus homologue of pUL21, bind the same hydrophobic groove on PP1 as RVxF and ϕϕ[xF] motifs, forming an extended β-sheet that bridges PP1 and the N-terminal domain of pUL21 or pORF38. Site-directed mutagenesis of both pUL2

SUBMITTER: Monkhouse H 

PROVIDER: S-EPMC12723162 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature