MIND複合体の構造は,酵母動体組立のための規制的焦点を定義する
Yoana N Dimitrova1, Simon Jenni1, Roberto Valverde1
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
Cell
|November 25, 2016
まとめ
MIND複合体はセントロメアとマイクロチューブルを結びつける. その構造は,Dsn1のリン酸化が,Mif2,COMA,およびNdc80複合体との相互作用を制御することによって,キネトコア組成を調節する方法を示しています.
科学分野:
- 細胞生物学
- 構造生物学
- 分子生物学
背景:
- キネトコアは,細胞分裂時にセントロメリックDNAをミクロチューブルに繋ぐ重要なタンパク質構造です.
- MIND複合体 (Mtw1, Nnf1, Nsl1, Dsn1) は,メタゾーン Mis12複合体と同様のキネトコアの重要な構成要素である.
- MINDは,ミクロチューブル結合のNdc80複合体とセントロメア・プロキシマル要素 (Mif2,COMA) を橋渡しする.
研究 の 目的:
- クライベロミセス・ラクティス・MIND複合体の結晶構造を決定する.
- キネトコア組立と微小管の結合におけるMINDの役割の基礎となる分子メカニズムを解明する.
- MINDがダイナミックなキネトコア形成のための規制信号を統合する方法を理解する.
主な方法:
- クライベロマイセス・ラクティスのMIND複合体の高解像度構造を取得するためのX線結晶学.
- タンパク質とタンパク質の相互作用と制御メカニズムを分析する生化学的測定法.
- 保存ドメインとインタラクションインターフェースの構造ベースの分析.
主要な成果:
- MINDコンプレックスは,長方形の非対称なY形の構造を採用し,2つの球状のヘッドと巻き巻き軸があります.
- N端のDsn1拡張は自己抑制ドメインとして作用し,Mif2/COMA結合を阻害する.
- Ipl1/Aurora BキナーゼによるDsn1のリン酸化は,自己抑制を緩和し,キネトコア組立を促進する.
- C端末のDsn1拡張はNdc80複合体のドッキングサイトとして機能する.
結論:
- MIND複合体の構造は,自己抑制とフォスフォ調節を通じて,キネトコア組立を調節する洗練されたメカニズムを示しています.
- Dsn1は,キネトコアのセントロメリックおよびマイクロチューブル結合成分を統合する上で中心的な役割を果たします.
- この研究は,キネトコア形成と微小管の結合のダイナミックなプロセスに関する原子レベルの洞察を提供します.
さらに関連する動画
関連する概念動画
02:57Attachment of Sister Chromatids
4.1K
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...
4.1K
01:32Assembly of Complex Microtubule Structures
2.8K
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.
2.8K
02:50Spindle Assembly
4.4K
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...
4.4K
02:19The Spindle Assembly Checkpoint
3.9K
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.9K
02:11Forces Acting on Chromosomes
4.0K
During mitosis, chromosome movements occur through the interplay of multiple piconewton level forces. In prometaphase, these forces help in chromosome assembly or congression at the equatorial plane, eventually leading to their alignment at the metaphase plate. The forces acting on the chromosomes are space and time-dependent; therefore, they vary with the position of the chromosomes as the cell progresses through mitosis.
Microtubules and motor proteins exert two types of forces on...
Microtubules and motor proteins exert two types of forces on...
4.0K
01:28Yeast Signaling
18.3K
Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
18.3K