Abstract
BackgroundThe histone fold is a common structural motif of proteins involved in the chromatin packaging of DNA and in transcription regulation. This single chain fold is stabilized by either homo- or hetero-dimer formation in archaea and eukarya. X-ray structures at atomic resolution have shown the eukaryotic nucleosome core particle to consist of a central tetramer of two bound H3-H4 dimers flanked by two H2A-H2B dimers. The c-terminal region of the H3 histone fold involved in coupling the two eukaryotic dimers of the tetramer, through a four-fold helical bundle, had previously been shown to be a region of reduced burial of hydrophobic residues within the dimers, and thereby provide a rationale for the observed reduced stability of the H3-H4 dimer compared with that of the H2A-H2B dimer. Furthermore, comparison between eukaryal and archaeal histones had suggested that this asymmetry in the distribution of hydrophobic residues along the H3 histone chains could be due to selective evolution that enhanced the coupling between the eukaryotic dimers of the tetramer.Results and discussionThe present work describes calculations utilizing the X-ray structures at atomic resolution of a hyperthermophile from Methanopyrus kandleri (HMk) and a eukaryotic transcription factor from Drosophila melanogaster (DRm), that are structurally homologous to the eukaryotic (H3-H4)2 tetramer. The results for several other related structures are also described. Reduced burial of hydrophobic residues, at the homologous H3 c-terminal regions of these structures, is found to parallel the burial at the c-terminal regions of the H3 histones and is, thereby, expected to affect dimer stability and the processes involving histone structural rearrangement. Significantly different sequence homology between the two histones of the HMk doublet with other archaeal sequences is observed, and how this might have occurred during selection to enhance tetramer stability is described.
Highlights
The histone fold is a common structural motif of proteins involved in the chromatin packaging of DNA and in transcription regulation
X-ray structures at atomic resolution, in either the absence [1] or presence of DNA [7], have shown the octamer of the eukaryotic nucleosome to be composed of histone dimers in a "handshake conformation" [1], with the H3-H4 dimers coupled forming a central tetramer flanked by two H2A-H2B dimers
The "c-terminal region" of the first hyperthermophile from Methanopyrus kandleri (HMk) histone is the region involved in the four-fold helical coupling that binds the HMk dimers of the tetramer
Summary
The histone fold is a common structural motif of proteins involved in the chromatin packaging of DNA and in transcription regulation This single chain fold is stabilized by either homoor hetero-dimer formation in archaea and eukarya. Side chain orientations in these regions while contributing to tetramer stability do not contribute to the stability of the dimers in the tetramer conformation by optimally burying residues within the dimer interiors Such orientations, if comparably maintained in the isolated dimers would, reduce dimer stability relative to that of dimers that are not required to perform such dual role of hydrophobic burial, namely, burial with respect to the interface between dimers as well as with respect to the dimer interiors. This has been proposed [8] as a rationale for the observed [9] reduced stability of the H3-H4 dimer compared with that of the H2A-H2B dimer
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