A pivot-tether model for nucleosome recognition by the chromosomal passenger complex

Area of Science:

• Cell Biology
• Molecular Biology
• Structural Biology

Background:

• Aurora B kinase activity is spatially restricted to H3pT3 nucleosomes near centromeres during mitosis.
• This localization is essential for spindle assembly checkpoint (SAC) signaling and chromosome biorientation.
• The chromosomal passenger complex (CPC), comprising survivin, borealin, and INCENP, mediates Aurora B binding to H3pT3 nucleosomes.

Purpose of the Study:

• To elucidate the structural mechanisms underlying CPC localization to H3pT3 nucleosomes.
• To understand how the CPC targeting module facilitates Aurora B's role in mitosis.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to determine the structure of the CPC targeting module bound to haspin-phosphorylated H3pT3 nucleosomes.
• Biochemical and functional assays were employed to assess the role of the identified structural features.

Main Results:

• The cryo-EM structure revealed how the N-terminus of borealin and the survivin BIR domain function as pivot and flexible tethering points.
• This arrangement enhances CPC affinity for H3pT3 nucleosomes while allowing for orientational flexibility.
• The study demonstrated the importance of this pivot-tether mechanism for Aurora B-mediated SAC signaling control.

Conclusions:

• The structural insights provide a mechanistic understanding of how the CPC precisely targets Aurora B kinase to specific chromatin regions.
• The flexible yet constrained pivot-tether arrangement is critical for regulating Aurora B activity and ensuring accurate chromosome segregation.
• This finding advances our knowledge of mitotic regulation and chromosome dynamics.