8q5h
From Proteopedia
Human KMN network (outer kinetochore)
Structural highlights
FunctionSPC24_HUMAN Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:14738735). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:14738735). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020).[1] [2] Publication Abstract from PubMedBiorientation of chromosomes during cell division is necessary for precise dispatching of a mother cell's chromosomes into its two daughters. Kinetochores, large layered structures built on specialized chromosome loci named centromeres, promote biorientation by binding and sensing spindle microtubules. One of the outer layer main components is a ten-subunit assembly comprising Knl1C, Mis12C and Ndc80C (KMN) subcomplexes. The KMN is highly elongated and docks on kinetochores and microtubules through interfaces at its opposite extremes. Here, we combine cryogenic electron microscopy reconstructions and AlphaFold2 predictions to generate a model of the human KMN that reveals all intra-KMN interfaces. We identify and functionally validate two interaction interfaces that link Mis12C to Ndc80C and Knl1C. Through targeted interference experiments, we demonstrate that this mutual organization strongly stabilizes the KMN assembly. Our work thus reports a comprehensive structural and functional analysis of this part of the kinetochore microtubule-binding machinery and elucidates the path of connections from the chromatin-bound components to the force-generating components. Structure of the human KMN complex and implications for regulation of its assembly.,Polley S, Raisch T, Ghetti S, Korner M, Terbeck M, Grater F, Raunser S, Aponte-Santamaria C, Vetter IR, Musacchio A Nat Struct Mol Biol. 2024 Jun;31(6):861-873. doi: 10.1038/s41594-024-01230-9. , Epub 2024 Mar 8. PMID:38459128[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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