9B2U

Haspin bound to H3 tail

Summary for 9B2U

• Entry DOI: 10.2210/pdb9b2u/pdb
• EMDB information: 44115
• Descriptor: Histone H3.2, Serine/threonine-protein kinase haspin (2 entities in total)
• Functional Keywords: haspin, nucleosome, histone, chromatin, h3t3ph, dna binding protein, dna binding protein-transferase complex, dna binding protein/transferase
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 2
• Total formula weight: 56146.61

Authors

Hicks, C.W.,Wolberger, C. (deposition date: 2024-03-16, release date: 2025-01-22, Last modification date: 2026-02-04)

Primary citation

Hicks, C.W.,Gliech, C.R.,Rahman, S.,Zhang, X.,Eneim, A.S.,Vasquez, S.J.,Holland, A.J.,Wolberger, C.
Haspin kinase binds to a nucleosomal DNA supergroove.
Nat.Struct.Mol.Biol., 32:1030-1037, 2025

PubMed Abstract: Phosphorylation of histone H3 threonine 3 (H3T3) by Haspin recruits the chromosomal passenger complex to the inner centromere and ensures proper cell cycle progression through mitosis. The mechanism by which Haspin binds to nucleosomes to phosphorylate H3T3 is not known. Here we report cryogenic electron microscopy structures of the human Haspin kinase domain bound to a nucleosome. In contrast with previous structures of histone-modifying enzymes, Haspin solely contacts the nucleosomal DNA, inserting into a supergroove formed by apposing major grooves of two DNA gyres. This binding mode provides a plausible mechanism by which Haspin can bind to nucleosomes in a condensed chromatin environment to phosphorylate H3T3. We identify key basic residues in the Haspin kinase domain that are essential for phosphorylation of nucleosomal histone H3 and binding to mitotic chromatin. Our structural data provide notable insight into a histone-modifying enzyme that binds to nucleosomes solely through DNA contacts.

PubMed: 39979508
DOI: 10.1038/s41594-025-01502-y

Experimental method

ELECTRON MICROSCOPY (3.64 Å)