COHESIN COMPLEX

粘连蛋白复合物

• 批准号: 7721142
• 负责人: DEBANANDA PATI
• 金额: $ 1.62万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721142
• 关键词: ATP phosphohydrolase; Anaphase; Aneuploidy; Binding; Biochemical; CSPG6 gene; Caliber; Cells; Cleaved cell; Complex; Computer Retrieval of Information on Scientific Projects Database; Core Protein; Cryoelectron Microscopy; DNA; Data; Endopeptidases; Funding; Goals; Grant; Head; Human Cell Line; Institution; Lead; Length; Metals; Metaphase; Modeling; Mutation; Protein Subunits; Research; Research Personnel; Resources; Saccharomycetales; Shadowing (Histology); Sister Chromatid; Source; United States National Institutes of Health; Upper arm; Vertebrates; cohesin; dimer; protein protein interaction; separase; three dimensional structure

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The cohesin complex holds the sister chromatids together after replication until metaphase and anaphase. It is composed of four core protein subunits in vertebrates, Rad21, SMC1, SMC3, SCC3 (SA1, SA2). The mass of cohesin complex is about 600 kDa. Sister chromatids are pulled apart when one cohesin subunit - SCC1/Rad21 - is cleaved by an endopeptidase called separase. Mutation of cohesin components may lead to delayed, premature and/or total inhibition of sister chromatid separation and result in aneuploidy. The N- and C-termini of both the SMC1 and SMC3 components are ABC-like ATPases , while the central region is a hinge domain, forming antiparallel intramolecular coiled coils. SMC1 and SMC3 also form a dimer via the hinge domain. The SMC1-SMC3 dimer looks like an open loop by metal-shadowing. The length of the SMC1-SMC3 heterodimer arm is about 60 nm. A cohesin ring model derived from studies on budding yeast seems reasonable (Gruber et al., 2003 Cell 112, 765-777). It suggests that SCC1/Rad21 C- and N-terminus bind to the ATPase heads of SMC1 and SMC3 heterodimer, respectively, to form a triangular ring. SCC3 then binds to reinforce the ring. Sister chromatids are surrounded by the ring (Uhlmann, 2004, Exp.Cell Res. 296, 80-85). However, according to the EM data, the maximum diameter of the ring is less than 35nm if the triangular ring can become a circle, which is not big enough to hold two 30 nm sister chromatids. We have studied the protein-protein interactions among the cohesin subunits in human cell lines. Our results indicate that cohesin complex is not a simple ring. To confirm our biochemical results, we are visualizing the complex by cryoEM. Our goal is to solve the 3-D structure of cohesin complex and to reveal how cohesin complex interact with DNA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在复制后，粘着蛋白复合体将姐妹染色单体保持在一起，直到中期和后期。在脊椎动物中，它由四个核心蛋白亚基组成：Rad 21、SMC 1、SMC 3、SCC 3（SA 1、SA 2）。黏连蛋白复合物的分子量约为600 kDa。当一个粘附素亚基-SCC 1/Rad 21-被称为分离酶的内肽酶切割时，姐妹染色单体被拉开。 粘连蛋白组分的突变可能导致姐妹染色单体分离的延迟、过早和/或完全抑制，并导致非整倍体。SMC 1和SMC 3的N-和C-末端都是ABC样ATP酶，而中心区域是铰链结构域，形成反平行的分子内卷曲螺旋。SMC 1和SMC 3也通过铰链结构域形成二聚体。SMC 1-SMC 3二聚体通过金属遮蔽看起来像开环。SMC 1-SMC 3异二聚体臂的长度为约60 nm。从芽殖酵母的研究中得到的粘附素环模型似乎是合理的（Gruber等人，2003 Cell 112，765-777）。这表明SCC 1/Rad 21的C端和N端分别与SMC 1和SMC 3异源二聚体的ATP酶头部结合，形成三角环。 然后SCC 3结合以加强环。 姐妹染色单体被环包围（Uhlmann，2004，Exp.Cell Res. 296，80-85）。 然而，根据EM数据，如果三角形环可以变成圆形，则环的最大直径小于35 nm，其不足以容纳两个30 nm的姐妹染色单体。我们已经研究了人类细胞系中粘附素亚基之间的蛋白质-蛋白质相互作用。我们的结果表明，cohesin复合物不是一个简单的环。为了确认我们的生化结果，我们正在通过cryoEM观察复合物。我们的目标是解决cohesin复合物的三维结构，并揭示cohesin复合物如何与DNA相互作用