Asymmetry in the burial of hydrophobic residues along the histone chains of eukarya, archaea and a transcription factor.
BACKGROUND
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 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.


CONCLUSIONS
The 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.
Silverman
B David
BD
IBM Thomas J. Watson Research Center, PO Box 218, Yorktown Heights, NY 10598, USA. silverma@us.ibm.com
D000818:Animals; D019843:Archaeal Proteins / Q000737:chemistry; D001703:Biophysics / Q000379:methods; D019281:Dimerization; D004331:Drosophila melanogaster; D019605:Euryarchaeota / Q000378:metabolism; D006657:Histones / Q000737:chemistry*; D008958:Models, Molecular; D015233:Models, Statistical; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry*
D019843:Archaeal Proteins; D006657:Histones; D009707:Nucleosomes; D014157:Transcription Factors