Crystal structure of the histone heterodimer containing histone variant H2A.W

Histone variant H2A.W plays a critical role in heterochromatin organization and genome stability, the loss of H2A.W can lead to heterochromatin decondensation, resulting in growth defects in flowering plants. Yet the mechanism underlying how H2A.W integrates into chromatin remains elusive. Here, we present the first high-resolution crystal structure of the Arabidopsis thaliana H2A.W (AtH2A.W) - Homo sapiens H2B (HsH2B) in the DNA-free heterodimeric state. In the structure, the global domain of DNA-free AtH2A.W-HsH2B share almost the same structure with its DNA bound form in the nucleosome, except the αC helix and the following C-terminal tail region (docking domain). What's more, we find that the AtH2A.W docking domain binds to the α2–α3 region of HsH2B, which is different from its role of interact with H3–H4 and DNA in nucleosome. These structure analyses suggest that the αC and docking domain of AtH2A.W is highly dynamic and may be remodeled during nucleosome assembly. In summary, our findings highlight the dynamic nature of AtH2A.W docking domain, providing mechanistic insight into how AtH2A.W integrates into chromatin and supports specialized chromatin functions. • Crystal structure of histone variant H2A.W–H2B at 1.8 Å. • The overall structure of the H2A.W–H2B heterodimer closely resembles that of H2A-containing nucleosomes. • The DNA-free H2A.W docking domain undergoes a ∼37 Å shift, adopting a protective conformation.