Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Structure of the Drosophila nucleosome core particle highlights evolutionary constraints on the H2A-H2B histone dimer.
Clapier CR
,
Chakravarthy S
,
Petosa C
,
Fernández-Tornero C
,
Luger K
,
Müller CW
.
???displayArticle.abstract???
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.
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.
Arents,
The nucleosomal core histone octamer at 3.1 A resolution: a tripartite protein assembly and a left-handed superhelix.
1991, Pubmed
Arents,
The nucleosomal core histone octamer at 3.1 A resolution: a tripartite protein assembly and a left-handed superhelix.
1991,
Pubmed
Barbera,
The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA.
2006,
Pubmed
,
Xenbase
Becker,
ATP-dependent nucleosome remodeling.
2002,
Pubmed
Bentley,
Crystal structure of the nucleosome core particle at 16 A resolution.
1984,
Pubmed
Boyer,
Molecular control of pluripotency.
2006,
Pubmed
Brünger,
Crystallography & NMR system: A new software suite for macromolecular structure determination.
1998,
Pubmed
Chakravarthy,
Structural characterization of the histone variant macroH2A.
2005,
Pubmed
,
Xenbase
Chothia,
The relation between the divergence of sequence and structure in proteins.
1986,
Pubmed
Collaborative Computational Project, Number 4,
The CCP4 suite: programs for protein crystallography.
1994,
Pubmed
Davey,
Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution.
2002,
Pubmed
,
Xenbase
Davey,
DNA-dependent divalent cation binding in the nucleosome core particle.
2002,
Pubmed
Dyer,
Reconstitution of nucleosome core particles from recombinant histones and DNA.
2004,
Pubmed
Finch,
Structure of nucleosome core particles of chromatin.
1977,
Pubmed
Fischle,
Histone and chromatin cross-talk.
2003,
Pubmed
Flores,
Comparison of conformational characteristics in structurally similar protein pairs.
1993,
Pubmed
Harp,
Asymmetries in the nucleosome core particle at 2.5 A resolution.
2000,
Pubmed
Hubbard,
Comparison of solvent-inaccessible cores of homologous proteins: definitions useful for protein modelling.
1987,
Pubmed
Jones,
Improved methods for building protein models in electron density maps and the location of errors in these models.
1991,
Pubmed
Khorasanizadeh,
The nucleosome: from genomic organization to genomic regulation.
2004,
Pubmed
Kornberg,
Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome.
1999,
Pubmed
Kornberg,
Chromatin structure; oligomers of the histones.
1974,
Pubmed
Kornberg,
Chromatin structure: a repeating unit of histones and DNA.
1974,
Pubmed
Lieberman,
Chromatin regulation of virus infection.
2006,
Pubmed
Luger,
Crystal structure of the nucleosome core particle at 2.8 A resolution.
1997,
Pubmed
Lund,
Epigenetics and cancer.
2004,
Pubmed
Narlikar,
Cooperation between complexes that regulate chromatin structure and transcription.
2002,
Pubmed
Richmond,
The structure of DNA in the nucleosome core.
2003,
Pubmed
Richmond,
Structure of the nucleosome core particle at 7 A resolution.
,
Pubmed
Russell,
Recognition of analogous and homologous protein folds: analysis of sequence and structure conservation.
1997,
Pubmed
Sullivan,
Characterization of sequence variability in nucleosome core histone folds.
2003,
Pubmed
Suto,
Crystal structure of a nucleosome core particle containing the variant histone H2A.Z.
2000,
Pubmed
,
Xenbase
Tsunaka,
Alteration of the nucleosomal DNA path in the crystal structure of a human nucleosome core particle.
2005,
Pubmed
,
Xenbase
White,
Structure of the yeast nucleosome core particle reveals fundamental changes in internucleosome interactions.
2001,
Pubmed
,
Xenbase
Workman,
Nucleosome displacement in transcription.
2006,
Pubmed