外部キネトコアDam1-Ndc80複合体の構造機構
Kyle W Muir1, Christopher Batters1, Tom Dendooven1
1MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Science (New York, N.Y.)
|December 7, 2023
まとめ
この研究は,キネトコアと微小管の結合の構造的基礎を,冷凍EMを用いて明らかにした. 細胞分裂中の染色体分離の精度には,キーインターフェースとDam1ステープルが不可欠です.
科学分野:
- 細胞生物学
- 分子生物学
- 構造生物学
背景:
- キネトコアは,細胞分裂中の正確な染色体分離に不可欠です.
- 誤差補正メカニズムは,キネトコアとマイクロチューブルの結合を調節する.
- キネトコア機能の基礎となる構造的メカニズムは完全に理解されていません.
研究 の 目的:
- マイクロチューブルと相互作用する外部のキネトコア複合体 (Ndc80とDam1) の構造的基礎を決定する.
- これらの複合体はどのように組み立てられ 調節されるかを明らかにする.
- キネトコア機能とエラー補正における特定の構造的特徴の役割を理解する.
主な方法:
- 複雑な構造を視覚化するための冷凍電子顕微鏡 (冷凍-EM).
- 酵母遺伝子は 鍵のインターフェースを 混乱させます
- 固定の安定性を測定する力破裂試験
主要な成果:
- マイクロチューブルのNdc80およびDam1リング複合体の冷凍-EM構造を決定した.
- 複雑な組み立てには,リング形成を容易にするDam1ステープルを含む複数のインターフェースが含まれます.
- キネトコアと微小管の結合と酵母菌の生存能力が損なわれた.
- 誤差補正用リン酸化部位は,重要なインターフェースで特定されました.
結論:
- 構造的な洞察は,キネトコア-マイクロチューブルの結合がどのように形成され,調節されているかを説明します.
- Dam1のステープルと特定のインターフェースは,安定で正確な染色体分離に不可欠です.
- 酸化部位は,固定部位を不安定化し,再設定するメカニズムを提供し,忠誠性を保証します.
関連する概念動画
02:57Attachment of Sister Chromatids
3.3K
As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules. Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall...
3.3K
02:50Spindle Assembly
3.7K
Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a...
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a...
3.7K
01:39Anaphase A and B
4.1K
Microtubules form through the end-to-end polymerization of tubulin heterodimers. Kinetochore microtubules originate from the spindle poles, and their plus-ends connect with the kinetochores on sister-chromatids. Ndc80 protein complexes, present on the kinetochore, form low-affinity links with the plus end of these kinetochore microtubules.
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
4.1K
01:32Assembly of Complex Microtubule Structures
1.8K
Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
1.8K
01:23Microtubule Formation
5.8K
Microtubules are dynamic structures that undergo continuous assembly and disassembly. They originate from specialized multi-protein complexes known as microtubule organizing centers or MTOCs. Within the MTOC, the point of origin of the microtubule is known as the minus end, while the end radiating outward is the plus end. Microtubules serve two primary functions — the organization of spindle complexes to separate sister chromatids during mitotic or meiotic cell division and the formation...
5.8K
01:45Destabilization of Microtubules
2.7K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.7K