XB-ART-36666Proteins April 1, 2008; 71 (1): 1-7.
Structure of the Drosophila nucleosome core particle highlights evolutionary constraints on the H2A-H2B histone dimer.
We determined the 2.45 A crystal structure of the nucleosome core particle from Drosophila melanogaster and compared it to that of Xenopus laevis bound to the identical 147 base-pair DNA fragment derived from human alpha-satellite DNA. Differences between the two structures primarily reflect 16 amino acid substitutions between species, 15 of which are in histones H2A and H2B. Four of these involve histone tail residues, resulting in subtly altered protein-DNA interactions that exemplify the structural plasticity of these tails. Of the 12 substitutions occurring within the histone core regions, five involve small, solvent-exposed residues not involved in intraparticle interactions. The remaining seven involve buried hydrophobic residues, and appear to have coevolved so as to preserve the volume of side chains within the H2A hydrophobic core and H2A-H2B dimer interface. Thus, apart from variations in the histone tails, amino acid substitutions that differentiate Drosophila from Xenopus histones occur in mutually compensatory combinations. This highlights the tight evolutionary constraints exerted on histones since the vertebrate and invertebrate lineages diverged.
PubMed ID: 17957772
PMC ID: PMC2443955
Article link: Proteins
Species referenced: Xenopus laevis
Genes referenced: h2ac21 h2bc21
Article Images: [+] show captions
|Figure 1. Sequence alignment of histones. Alignment of histones from Drosophila (Dm), Xenopus (Xl), chicken (Gg), mouse (Mm), human (Hs), and yeast (Sc). Drosophila H2A, H2B, H3, H4 sequences correspond to accession codes NP_724343, NP_724342, NP_724345, NP_724344, respectively. Only residues that differ from the Drosophila sequence are shown. Amino acid substitutions that differentiate the Drosophila and Xenopus histone core regions are highlighted in yellow and cyan; those in ordered tail residues are highlighted in pink. Unstructured residues are indicated in lower case.|
|Figure 2. Structural differences within the H2A and H2B histone tails between Dm-NCP147 and Xla-NCP147. (a) Dm-NCP viewed along the superhelix showing the location of the N-terminal tail of H2A. (b) The N-terminal histone tail of H2A′, showing close-up of boxed region in a. Side chains from Drosophila are in light gray; from Xenopus in dark Grey. Hydrogen bonds unique to Drosophila are in black; those unique to Xenopus are in red. Residue substitutions are labelled in the direction from Xenopus to Drosophila. DNA bases are shown as sticks, except for Thy45. The view is slightly rotated relative to that in a. (c) Edge view of the NCP showing location of the Nterminal tail of H2B. (d) Histone tail of H2B′ showing close-up view of boxed region in c. Base atoms is shown for Thy50 and Cyt-49.|
|Figure 3. Structural differences in the H2A-H2B dimer between Dm-NCP147 and Xla-NCP147. (a) Overview of structured residues in the hydrophobic core of the H2A-H2B dimer that diverge between Xenopus and Drosophila. View is approximately along the pseudodyad. (b) Compensatory changes within the hydrophobic core of H2A. Residue substitutions are labeled in the direction from Xenopus to Drosophila. (c) Compensatory changes involving two residues in the H2A-H2B dimer interface. The hydrogen bond missing from the Dm structure is in red. (d) Compensatory changes involving three residues in the H2A-H2B dimer interface.|
References [+] :
, The CCP4 suite: programs for protein crystallography. 2004, Pubmed