23AG

Crystal structure of BAZ2A in complex with an S-HDAg_K72ac peptide

Summary for 23AG

• Entry DOI: 10.2210/pdb23ag/pdb
• Descriptor: Bromodomain adjacent to zinc finger domain protein 2A, Small delta antigen (3 entities in total)
• Functional Keywords: baz2a, bromodomain, acetylated peptide, protein peptide interaction, s-hdag, hepatitis delta antigen, lysine acetylation, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 13474.09

Authors

Liu, Y.L.,Lv, M.J.,Shang, X.C. (deposition date: 2026-01-29, release date: 2026-08-12)

Primary citation

Hu, H.,Lv, M.,Wang, X.,Shang, X.,Wu, Q.,Chen, Y.,Zhou, Y.,Huang, Q.,Jiang, T.,Qin, S.,Huang, X.,Zhang, Z.,Xu, G.,Liu, Y.
Structural insights into histone mimicry by the small hepatitis delta antigen.
J.Biol.Chem., 302:113252-113252, 2026

PubMed Abstract: Hepatitis delta virus (HDV) is a satellite RNA virus that requires hepatitis B virus (HBV) for propagation but replicates its genome independently in the nucleus. The small form of the hepatitis delta antigen (S-HDAg) is essential for replication and is regulated by post-translational modifications. Acetylation at lysine 72 (K72ac) enables S-HDAg to interact with the bromodomain (BRD) of the host chromatin remodeler bromodomain adjacent to zinc finger domain protein 2B (BAZ2B) to promote viral replication. However, the structural basis for this interaction has remained elusive. Here, we provide structural and biophysical insights into this interaction through quantitative binding assays and X-ray crystallography. Isothermal titration calorimetry revealed that BRDs of BAZ2B and its close homolog BAZ2A bind to the viral peptide weakly, with BAZ2A-BRD exhibiting a modestly higher affinity. The crystal structure of BAZ2A-BRD in complex with the S-HDAg-K72ac peptide demonstrates an inverted binding orientation relative to canonical histone ligands, rationalizing the weak interaction. Mutagenesis studies confirmed the critical binding interface both in vitro and in cells. These findings elucidate the molecular mechanism by which HDV co-opts host BAZ2 bromodomains via a unique, weak-affinity interaction, providing a structural framework for understanding viral replication.

PubMed: 42285512
DOI: 10.1016/j.jbc.2026.113252

Experimental method

X-RAY DIFFRACTION (1.61 Å)