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Structure and binding of the H4 histone tail and the effects of lysine 16 acetylation.

Publication ,  Journal Article
Yang, D; Arya, G
Published in: Physical chemistry chemical physics : PCCP
February 2011

The H4 histone tail plays a critical role in chromatin folding and regulation--it mediates strong interactions with the acidic patch of proximal nucleosomes and its acetylation at lysine 16 (K16) leads to partial unfolding of chromatin. The molecular mechanism associated with the H4 tail/acidic patch interactions and its modulation via K16 acetylation remains unknown. Here we employ a combination of molecular dynamics simulations, molecular docking calculations, and free energy computations to investigate the structure of the H4 tail in solution, the binding of the H4 tail with the acidic patch, and the effects of K16 acetylation. The H4 tail exhibits a disordered configuration except in the region Ala15-Lys20, where it exhibits a strong propensity for an α-helical structure. This α-helical region is found to dock very favorably into the acidic patch groove of a nucleosome with a binding free energy of approximately -7 kcal mol(-1). We have identified the specific interactions that stabilize this binding as well as the associated energetics. The acetylation of K16 is found to reduce the α-helix forming propensity of the H4 tail and K16's accessibility for mediating external interactions. More importantly, K16 acetylation destabilizes the binding of the H4 tail at the acidic patch by mitigating specific salt bridges and longer-ranged electrostatic interactions mediated by K16. Our study thus provides new microscopic insights into the compaction of chromatin and its regulation via posttranslational modifications of histone tails, which could be of interest to chromatin biology, cancer, epigenetics, and drug design.

Duke Scholars

Published In

Physical chemistry chemical physics : PCCP

DOI

EISSN

1463-9084

ISSN

1463-9076

Publication Date

February 2011

Volume

13

Issue

7

Start / End Page

2911 / 2921

Related Subject Headings

  • Thermodynamics
  • Protein Structure, Secondary
  • Protein Binding
  • Molecular Dynamics Simulation
  • Lysine
  • Hydrogen-Ion Concentration
  • Histones
  • Chemical Physics
  • Acetylation
  • 51 Physical sciences
 

Citation

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Yang, D., & Arya, G. (2011). Structure and binding of the H4 histone tail and the effects of lysine 16 acetylation. Physical Chemistry Chemical Physics : PCCP, 13(7), 2911–2921. https://doi.org/10.1039/c0cp01487g
Yang, Darren, and Gaurav Arya. “Structure and binding of the H4 histone tail and the effects of lysine 16 acetylation.Physical Chemistry Chemical Physics : PCCP 13, no. 7 (February 2011): 2911–21. https://doi.org/10.1039/c0cp01487g.
Yang D, Arya G. Structure and binding of the H4 histone tail and the effects of lysine 16 acetylation. Physical chemistry chemical physics : PCCP. 2011 Feb;13(7):2911–21.
Yang, Darren, and Gaurav Arya. “Structure and binding of the H4 histone tail and the effects of lysine 16 acetylation.Physical Chemistry Chemical Physics : PCCP, vol. 13, no. 7, Feb. 2011, pp. 2911–21. Epmc, doi:10.1039/c0cp01487g.
Yang D, Arya G. Structure and binding of the H4 histone tail and the effects of lysine 16 acetylation. Physical chemistry chemical physics : PCCP. 2011 Feb;13(7):2911–2921.
Journal cover image

Published In

Physical chemistry chemical physics : PCCP

DOI

EISSN

1463-9084

ISSN

1463-9076

Publication Date

February 2011

Volume

13

Issue

7

Start / End Page

2911 / 2921

Related Subject Headings

  • Thermodynamics
  • Protein Structure, Secondary
  • Protein Binding
  • Molecular Dynamics Simulation
  • Lysine
  • Hydrogen-Ion Concentration
  • Histones
  • Chemical Physics
  • Acetylation
  • 51 Physical sciences