Extended string-like binding of the phosphorylated HP1? N-terminal tail to the lysine 9-methylated histone H3 tail.

ABSTRACT: The chromodomain of HP1? binds directly to lysine 9-methylated histone H3 (H3K9me). This interaction is enhanced by phosphorylation of serine residues in the N-terminal tail of HP1? by unknown mechanism. Here we show that phosphorylation modulates flexibility of HP1?'s N-terminal tail, which strengthens the interaction with H3. NMR analysis of HP1?'s chromodomain with N-terminal tail reveals that phosphorylation does not change the overall tertiary structure, but apparently reduces the tail dynamics. Small angle X-ray scattering confirms that phosphorylation contributes to extending HP1?'s N-terminal tail. Systematic analysis using deletion mutants and replica exchange molecular dynamics simulations indicate that the phosphorylated serines and following acidic segment behave like an extended string and dynamically bind to H3 basic residues; without phosphorylation, the most N-terminal basic segment of HP1? inhibits interaction of the acidic segment with H3. Thus, the dynamic string-like behavior of HP1?'s N-terminal tail underlies the enhancement in H3 binding due to phosphorylation.

SUBMITTER: Shimojo H 

PROVIDER: S-EPMC4776139 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature