9MLS
GammaH2AX containing nucleosome, Extended (Class 3)
Summary for 9MLS
| Entry DOI | 10.2210/pdb9mls/pdb |
| EMDB information | 48379 |
| Descriptor | Histone H3.1, Histone H4, Histone H2AX, ... (6 entities in total) |
| Functional Keywords | phosphorylation, nucleosome, nucleosome stacking, nuclear protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 10 |
| Total formula weight | 211417.37 |
| Authors | |
| Primary citation | Panigrahi, R.,Edwards, R.,Islam, M.T.,Lu, J.,Kulepa, A.,Kim, T.H.,Mark Glover, J.N. Structural insights into gamma H2Ax containing nucleosomes. Nucleic Acids Res., 53:-, 2025 Cited by PubMed Abstract: The phosphorylation of the histone variant H2AX on the nucleosome, yielding γH2AX, acts as a 'master control switch', signaling the recruitment of DNA repair factors at DNA double-stranded break sites. This phosphorylation is recognized by BRCA1 carboxy-terminal (BRCT) domains of specific repair proteins. Using cryogenic electron microscopy (cryo-EM), we provide structural insights into diverse mononucleosome architectures and inter-nucleosomal interactions in the presence of H2AX, mimicking nucleosomes during DNA repair. We resolved three distinct stacked structures where the nucleosomal dyad axes and disk planes align parallel. The inter-nucleosomal interactions involve unique contacts mediated by the H4 N-terminal tail, exposed H2B elements, and DNA. Geometric analysis of stacking constraints, including published structures, reveals a tight distribution of rotational parameters around 0o, with the greatest variability in the translational parameter 'slide'. Our studies indicate that phosphorylation-dependent binding of BRCT domains with γH2AX nucleosomes disrupts stacking. However, no clear densities for BRCT proteins were observed, indicative of dynamic interactions. Molecular simulations replicate the stability of BRCT binding to γH2AX but do not indicate stable docked conformations of BRCT to nucleosome. We propose that BRCT recognition of γH2AX nucleosomes could contribute to chromatin decondensation during DNA damage signaling, exposing the nucleosomal acidic patch for repair factor recognition. PubMed: 41123210DOI: 10.1093/nar/gkaf1028 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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