Phosphorylation of shiftless is important for inhibiting the programmed -1 ribosomal frameshift.

ABSTRACT: Shiftless (SFL) is a broad-spectrum inhibitor of programmed -1 ribosomal frameshift (-1 PRF) and exhibits various antiviral activities. Here, we characterized human SFL structurally and biochemically. The 2.0-angstrom resolution crystal structure of SFL reveals a boat-like module comprising an N-terminal helical bundle and three zinc fingers at the C terminus. A hyperphosphorylation loop (HPL) buried between the helical bundle and the zinc finger 1 harbors four phosphorylated residues (p-S249, p-T250 p-T253, and p-S256), which are important to protein folding. SFL forms monomers in solution and binds the HIV-1 -1 PRF sequence with nanomolar affinity (K_D = 5.7 nanomolar). Disruption of HPL phosphorylation decreased the RNA binding affinity and undermined the SFL-mediated -

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12716391 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature