H1 linker histones are involved in chromatin structure and gene regulation. The carboxy-terminal domain (CTD) of histone H1 is very basic with ~40% Lys residues, ~75% of which are present as doublets. The CTD has little structure in diluted solution but becomes cooperatively folded upon interaction with DNA. The DNA-bound CTD contains α-helix, β-structure, turns, and flexible regions. We studied the effects of charge neutralization on the secondary structure of the CTD independently of DNA interaction through deprotonation of the ε-amino groups of the Lys side chains at alkaline pH. Alkaline pH induces extensive folding of the CTD with proportions of secondary structure similar to those observed in the complexes with DNA. The CTD is phosphorylated by cyclin-dependent kinases. In the fully phosphorylated CTD, alkaline pH induces a higher amount of beta-sheet and a lower amount of α-helix, as observed in the complexes with DNA. These results, together with structure predictions, suggest that the increased hydrophobicity of Lys side chains accompanying charge neutralization is responsible for the folding of the CTD upon interaction with DNA. © 2009 American Chemical Society.
|Journal||Journal of Physical Chemistry B|
|Publication status||Published - 3 Sep 2009|