9SI3

Chromosomal Passenger Complex in complex with H3T3ph Nucleosome

Summary for 9SI3

• Entry DOI: 10.2210/pdb9si3/pdb
• EMDB information: 54924
• Descriptor: Borealin, Histone H3.2, Histone H4, ... (9 entities in total)
• Functional Keywords: nucleosome-binding dna-binding stabilising nucleosome acidic-patch interaction, cell cycle
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 14
• Total formula weight: 384260.05

Authors

Gireesh, A.,Abad, M.A.,Sotelo-Parrilla, P.,Jeyaprakash, A.A. (deposition date: 2025-08-28, release date: 2025-10-01, Last modification date: 2025-11-26)

Primary citation

Gireesh, A.,Abad, M.A.,Nozawa, R.S.,Sotelo-Parrilla, P.,Dury, L.C.,Likhodeeva, M.,Wear, M.,Spanos, C.,Peralta, C.C.,Rappsilber, J.,Hopfner, K.P.,Wilson, M.D.,Vanderlinden, W.,Hirota, T.,Jeyaprakash, A.A.
Nucleosome interaction of the CPC secures centromeric chromatin integrity and chromosome segregation fidelity.
Embo J., 44:6556-6597, 2025

PubMed Abstract: The chromosomal passenger complex (CPC; Borealin-Survivin-INCENP-Aurora B kinase) ensures accurate chromosome segregation by orchestrating sister chromatid cohesion, error correction of kinetochore-microtubule attachments, and spindle assembly checkpoint signaling. Correct spatiotemporal regulation of CPC is critical for its function. Phosphorylations of histone H3 Thr3 and histone H2A Thr120 and modification-independent nucleosome interactions involving Survivin and Borealin contribute to CPC centromere enrichment. However, how various nucleosome binding elements collectively contribute to CPC centromere enrichment at the mechanistic level, and whether CPC has any non-catalytic role at centromere remain open questions. Combining the high-resolution cryo-EM structure of a CPC-bound H3Thr3ph nucleosome with atomic force microscopy and biochemical and cellular assays, we demonstrate that CPC employs multipartite interactions, which facilitate its engagement with nucleosome acidic patch and the DNA entry-exit site. Perturbing the CPC-nucleosome interaction compromises chromatin protection against MNase digestion in vitro, and centromeric chromatin stability and error-free chromosome segregation in cells. Our work suggests a non-catalytic chromatin-stabilizing role of CPC in maintaining centromeric chromatin features critical for kinetochore function.

PubMed: 41145915
DOI: 10.1038/s44318-025-00594-y

Experimental method

ELECTRON MICROSCOPY (2.83 Å)