Bipartite binding interface recruiting HP1 to chromosomal passenger complex at inner centromeres

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Mitotic fidelity relies on Aurora B kinase activity, part of the chromosomal passenger complex (CPC).
• HP1 proteins are crucial for enriching the CPC at inner centromeres.
• HP1 interaction with INCENP, a CPC component, is key for this enrichment.

Purpose of the Study:

• To elucidate the molecular mechanism behind HP1 and INCENP interaction.
• To identify the specific domains and motifs involved in HP1 binding to INCENP.
• To understand how this interaction contributes to centromeric HP1 enrichment and mitotic fidelity.

Main Methods:

• Biochemical assays to study protein-protein interactions.
• Structural biology techniques to analyze domain folding and binding.
• Cellular localization studies to confirm HP1 enrichment at centromeres.

Main Results:

• The interaction between INCENP and HP1 requires both the PVI motif and a C-terminal domain.
• These domains conditionally fold into a β-strand and α-helix upon HP1 binding, forming the SSH domain.
• The SSH domain is necessary and sufficient for high-affinity HP1-INCENP interaction and HP1 centromeric localization.

Conclusions:

• A novel bipartite binding module, the SSH domain, mediates HP1 interaction with INCENP.
• This interaction is essential for HP1 enrichment at inner centromeres.
• The findings highlight a new mechanism ensuring Aurora B activity and mitotic fidelity.