3AZI: Crystal Structure Of Human Nucleosome Core Particle Containing H4k31q Mutation

Citation:
Abstract
Post-translational modifications (PTMs) of histones play important roles in regulating the structure and function of chromatin in eukaryotes. Although histone PTMs were considered to mainly occur at the N-terminal tails of histones, recent studies have revealed that PTMs also exist in the histone-fold domains, which are commonly shared among the core histones H2A, H2B, H3, and H4. The lysine residue is a major target for histone PTM, and the lysine to glutamine (KQ) substitution is known to mimic the acetylated states of specific histone lysine residues in vivo. Human histones H3 and H4 contain 11 lysine residues in their histone-fold domains (five for H3 and six for H4), and eight of these lysine residues are known to be targets for acetylation. In the present study, we prepared 11 mutant nucleosomes, in which each of the lysine residues of the H3 and H4 histone-fold domains was replaced by glutamine: H3 K56Q, H3 K64Q, H3 K79Q, H3 K115Q, H3 K122Q, H4 K31Q, H4 K44Q, H4 K59Q, H4 K77Q, H4 K79Q, and H4 K91Q. The crystal structures of these mutant nucleosomes were determined at 2.4-3.5 A resolutions. Some of these amino acid substitutions altered the local protein-DNA interactions and the interactions between amino acid residues within the nucleosome. Interestingly, the C-terminal region of H2A was significantly disordered in the nucleosome containing H4 K44Q. These results provide an important structural basis for understanding how histone modifications and mutations affect chromatin structure and function.
PDB ID: 3AZIDownload
MMDB ID: 93651
PDB Deposition Date: 2011/5/25
Updated in MMDB: 2011/09
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 3AZI: decameric; determined by author and by software (PISA)
Molecular Components in 3AZI
Label Count Molecule
Proteins (8 molecules)
2
Histone H3.1(Gene symbol: HIST1H3A)
Molecule annotation
2
Histone H4(Gene symbol: HIST1H4I)
Molecule annotation
2
Histone H2A Type 1-be(Gene symbol: HIST1H2AE)
Molecule annotation
2
Histone H2B Type 1-J(Gene symbol: HIST1H2BJ)
Molecule annotation
Nucleotide(1 molecule)
2
146-mer DNA
Molecule annotation
Chemicals (17 molecules)
1
4
2
13
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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