8Q5H

Human KMN network (outer kinetochore)

8Q5H の概要

• エントリーDOI: 10.2210/pdb8q5h/pdb
• EMDBエントリー: 18179
• 分子名称: Kinetochore protein Spc24, Kinetochore protein Spc25, Protein MIS12 homolog, ... (7 entities in total)
• 機能のキーワード: outer kinetochore, kmn, complex, cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 185973.55

構造登録者

Raisch, T.,Polley, S.,Vetter, I.,Musacchio, A.,Raunser, S. (登録日: 2023-08-09, 公開日: 2024-02-14, 最終更新日: 2025-07-09)

主引用文献

Polley, S.,Raisch, T.,Ghetti, S.,Korner, M.,Terbeck, M.,Grater, F.,Raunser, S.,Aponte-Santamaria, C.,Vetter, I.R.,Musacchio, A.
Structure of the human KMN complex and implications for regulation of its assembly.
Nat.Struct.Mol.Biol., 31:861-873, 2024

PubMed Abstract: Biorientation 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.

PubMed: 38459128
DOI: 10.1038/s41594-024-01230-9

実験手法

ELECTRON MICROSCOPY (4.5 Å)