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Biophys J. 2008 Jun;94(12):4579-85. doi: 10.1529/biophysj.107.115824. Epub 2008 Jan 11.

Effects of posttranslational modifications on the structure and dynamics of histone H3 N-terminal Peptide.

Author information

1
UC Davis Genome Center and Department of Applied Science, University of California, Davis, California 95616, USA.

Abstract

The highly conserved signature N-terminal peptide of histone protein H3 plays crucial roles in gene expression controls. We investigated the conformational changes of the peptide caused by lysine dimethylation and acetylation of the histone H3 N-terminal tail by molecular dynamics and replica-exchange molecular dynamics simulations. Our results suggest that the most populated structures of the modified H3 N-terminal peptides are very similar to those of the wild-type peptide. Thus, the modifications introduce marginal changes to the most favorable conformations of the peptides. However, the modifications have significant effects on the stabilities of the most populated states that depend on the modifications. Whereas dimethylation of lysine 4 or lysine 9 alone tends to stabilize the most populated states, double dimethylation and acetylation of both lysine 4 and lysine 9 reduce both the helical conformation and the stability of the most populated states significantly. The calculated melting temperatures showed that the doubly acetylated peptide has the lowest melting temperature (T(m) = 324 K), which is notably lower than the melting temperatures of the other four peptides (T(m) approximately 346-350 K). In light of the existing experimental evidence, we propose that the changes in the dynamics of the modified variants contribute to their different functional roles.

PMID:
18192367
PMCID:
PMC2397375
DOI:
10.1529/biophysj.107.115824
[Indexed for MEDLINE]
Free PMC Article

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