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TitleA pivot-tether model for nucleosome recognition by the chromosomal passenger complex.
Journal, issue, pagesEMBO Rep, Vol. 26, Issue 17, Page 4219-4247, Year 2025
Publish dateJul 15, 2025
AuthorsReinis R Ruza / Chyi Wei Chung / Danny B H Gold / Michela Serena / Emile Roberts / Ulrike Gruneberg / Francis A Barr /
PubMed AbstractSpatial restriction of Aurora B to T3-phosphorylated histone H3 (H3pT3) nucleosomes adjacent to centromeres during prometaphase and metaphase enables it to phosphorylate proteins necessary for ...Spatial restriction of Aurora B to T3-phosphorylated histone H3 (H3pT3) nucleosomes adjacent to centromeres during prometaphase and metaphase enables it to phosphorylate proteins necessary for spindle assembly checkpoint signalling and biorientation of chromosomes on the mitotic spindle. Aurora B binding to H3pT3-nucleosomes requires a multivalent targeting module, the chromosomal passenger complex (CPC), consisting of survivin, borealin, and INCENP. To shed light on how these components mediate CPC localisation during prometaphase and metaphase, we determined the structure of the CPC targeting module in complex with haspin-phosphorylated H3pT3-nucleosomes by cryo-electron microscopy. This structure shows how the N-terminus of borealin and the survivin BIR domain act as pivot and flexible tethering points, respectively, to increase CPC affinity for H3pT3 nucleosomes without limiting it to a specific orientation. We demonstrate that this flexible, yet constrained pivot-tether arrangement is important for the control of spindle assembly checkpoint signalling by Aurora B.
External linksEMBO Rep / PubMed:40664717 / PubMed Central
MethodsEM (single particle)
Resolution2.29 - 6.9 Å
Structure data

EMDB-19513, PDB-8rup:
Chromosome Passenger Complex (CPC) localization module in complex with H3.T3p-nucleosome
Method: EM (single particle) / Resolution: 2.42 Å

EMDB-19514, PDB-8ruq:
Borealin N-terminus in complex with H3.T3p-nucleosome
Method: EM (single particle) / Resolution: 2.29 Å

EMDB-19684: Chromosome Passenger Complex (CPC) localization module in complex with H3.T3p-nucleosome - focused refinement of the distal end of CPC
Method: EM (single particle) / Resolution: 6.9 Å

EMDB-19685: Chromosome Passenger Complex (CPC) localization module in complex with H3.T3p-nucleosome - raw concensus map
Method: EM (single particle) / Resolution: 2.4 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)
  • unidentified (others)
KeywordsCELL CYCLE / CPC / nucleosome / chromosome segregation / histone modification / cryoEM

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