ヒトのキネトコアの構造に対する生化学的再構成からの洞察
John R Weir1, Alex C Faesen1, Kerstin Klare1
1Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany.
Nature
|September 1, 2016
まとめ
この研究では,CHIKMLN複合体が中心タンパク質A (CENP-A) 核細胞に選択的に結合し,細胞分裂中の染色体分離の鍵となる結合を形成することを明らかにした. この発見は,真核生物におけるキネトコア構造と機能を明らかにする.
科学分野:
- 細胞生物学
- 分子生物学
- 遺伝学
背景:
- 細胞分裂の過程で正確な染色体分離は生命にとって不可欠であり,染色体をミトーシス・スピンドルに繋ぐためにキネトコアに依存しています.
- キネトコアは,CENP-Aヌクレオソームで濃縮されたセントロメアで組み立てられ,内側 (CCAN) と外側 (KMNネットワーク) の複合体を含む.
- CCANの組織とその選択的なCENP-Aの認識に関する以前の理解は不完全でした.
研究 の 目的:
- 構成センターアソシエイトネットワーク (CCAN) の組織的原則と,CENP-Aの承認におけるその役割について説明する.
- 標準のH3核分裂体よりもCENP-A核分裂体の選択的結合にCCANがどのように寄与するかを理解する.
主な方法:
- バイオケミカルな再構成により,キネトコア複合体の構成と相互作用が研究されました.
- CENP-A核分裂体に対するCCAN亜複合体の結合選択性を調査した.
主要な成果:
- 7つのサブユニットからなるCCANサブ複合体であるCHIKMLN複合体は,選択的なCENP-A核細胞結合に不可欠であると特定された.
- CENP-A:CHIKMLN複合体は,KMNネットワークを直接結合し,21つのサブユニット最小複合体を形成します.
- この複合体は,CENP-A核体と微小管体間の高親和関係をin vitroで確立する.
結論:
- この発見は,キネトコア-マイクロチューブル結合の基本的な構造モジュールを示しています.
- このモジュールはエウカリオット全体に保存され,ポイント対地域キネトコアの進化を潜在的に説明します.
- 生化学的復元は,将来のメカニズム的および定量的なキネトコア研究のための基礎を提供します.
関連する概念動画
02:57Attachment of Sister Chromatids
4.2K
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...
4.2K
01:18Assembly of Cytoskeletal Filaments
28.2K
Cytoskeletal filaments are polymeric forms of smaller protein subunits. However, individual cytoskeletal filaments may easily disassemble or associate with other similar filaments to form rigid structures. Microfilaments, made of actin monomers, rely on actin-binding proteins to form bundles and create networks of individual actin filaments. Microtubules rely on microtubule-associated proteins (MAPs) to form sturdy cylindrical structures. However, the proteins involved in forming complex...
28.2K
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
01:35Disassembly of Intermediate Filaments
2.8K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.8K
01:39Anaphase A and B
5.7K
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...
5.7K
02:27The Mitotic Spindle
8.3K
The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures...
The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures...
8.3K