The MIS12 complex is a protein interaction hub for outer kinetochore assembly.

Area of Science:

• Cell Biology
• Molecular Biology
• Structural Biology

Background:

• Kinetochores are critical protein structures for chromosome segregation during mitosis.
• The KMN network, comprising NDC80, MIS12, and KNL1 complexes, forms the outer kinetochore interface for microtubule attachment.
• Previous work elucidated the structure of the human NDC80 complex.

Purpose of the Study:

• To determine the structural organization and subunit interactions of the human MIS12 complex.
• To investigate how the MIS12 complex integrates with the broader KMN network.
• To understand the role of specific subunits in mediating these interactions.

Main Methods:

• Biochemical analysis
• Cross-linking mass spectrometry
• Negative-stain electron microscopy

Main Results:

• The human MIS12 complex exhibits an elongated structure, approximately 22 nm in length.
• The NSL1 subunit was identified as a key scaffold, mediating interactions between the MIS12 complex and both the NDC80 and KNL1 complexes.
• Detailed subunit organization and reciprocal contacts within the MIS12 complex were elucidated.

Conclusions:

• The structural and interaction data provide a molecular basis for the MIS12 complex's role within the KMN network.
• NSL1's scaffolding function is crucial for kinetochore assembly and function.
• Findings advance the understanding of kinetochore architecture and its conservation across organisms.