什么AlphaFold告诉我们关于凝聚素在染色体上的保留和释放
Kim A Nasmyth1, Byung-Gil Lee2, Maurici Brunet Roig1
1Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
eLife
|November 17, 2023
概括
这项研究提出了关于凝聚素释放和稳定性的新假设,利用AlphaFold 2预测. 这些发现阐明了Wapl,Sororin和乙化在调节DNA拓和姐妹染色体凝聚力的作用.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 是一个遗传学.
背景情况:
- 凝聚蛋白组织DNA拓和姐妹染色体凝聚力.
- 瓦普尔和索罗林调节凝聚蛋白的染色质结合和释放.
- 之前,Wapl诱导释放和Sororin介导阻断的机制是未知的.
研究的目的:
- 为Wapl诱导的凝聚素释放和Sororin介导的稳定性的分子机制提出可测试的假设.
- 阐明通过Wapl,Sororin,Pds5和乙化对凝聚素调节的结构基础.
主要方法:
- 使用AlphaFold 2进行三维蛋白质结构预测.
- 分析了蛋白质复合体的形成和相互作用.
- 根据拟议的结构,解释现有的突变表型.
主要成果:
- 提出了Wapl,SA,Pds5和Scc1的N端域 (NTD) 的四元复合体.
- 揭示了Wapl如何通过一个保存的裂将Scc1的NTD隔离起来.
- 解释了Smc1/Smc3解离,Esco招募以及Sororin在Smc3/Scc1接口上的抑制性结合.
结论:
- 结构假设解释了Wapl在凝聚素释放中的作用和Sororin在稳定中的作用.
- 这些发现为理解凝聚力动态和监管提供了一个框架.
- 拟议的机制得到了现有遗传数据的支持,并且具有高度可测试性.
相关概念视频
Cohesins
4.5K
Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In mitosis, all cohesin complexes present on the chromosomes are removed before the start of the anaphase stage.
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of...
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of...
4.5K
Separation of Sister Chromatids
3.7K
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
3.7K
Condensins
3.5K
Condensins are large protein complexes that use ATP to fuel the assembly of chromosomes during mitosis. They transform the tangled, shapeless mass of post-interphase DNA into individualized chromosomes by compacting, organizing, and segregating chromosomal DNA.
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...
3.5K
Attachment 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
Restarting Stalled Replication Forks
5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K
Adaptability of Cytoskeletal Filaments
3.7K
The cytoskeleton is a complex dynamic structure performing varied functions based on cellular requirements. The adaptability of the individual filaments in the cytoskeleton determines their ability to perform various functions within the cell. It can undergo rapid reorganization during processes like cell division or remain stable for several hours as in the interphase. The adaptability of these filaments depends on stringent regulatory mechanisms. The microfilament and microtubules of the...
3.7K


