STRUCTURE OF A CED-4-CED-3 HOLOENZYME

CED-4-CED-3 全酶的结构

• 批准号: 8170635
• 负责人: YIGONG SHI
• 金额: $ 0.34万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170635
• 关键词: Apoptosis; Binding; Caenorhabditis elegans; Caspase; Cell Death; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Differentiation and Growth; Funding; Genes; Grant; Holoenzymes; Homeostasis; Homo sapiens; Institution; Molecular; Pathway interactions; Play; Recruitment Activity; Research; Research Personnel; Resources; Role; Source; Structure; United States National Institutes of Health; cell killing; monomer

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. Apoptosis plays a central role in the development and homeostasis of metazoans. The fundamental significance of apoptosis as an intrinsic component of growth and differentiation was only realized in the last decade, with the discovery of the cell death pathway first in Caenorhabditis elegans (C. elegans) and then in homo sapiens. Bob Horvitz and his colleagues at MIT were responsible for the isolation and characterization of four genes (egl-1, ced-9, ced-4, and ced-3) that collectively control the onset of programmed cell death in C. elegans. CED-3 is the cell-killing caspase and its activation requires CED-4. However, how CED-4 facilitates the activation of CED-3 remains completely unknown. We have recently shown that CED-4 forms an octameric apoptosome, which only recruits two molecules of the CED-3 monomer for activation. The activated CED-3 remains bound to the CED-4 apoptosome as a holoenzyme. We have crystallized the CED-4-CED-3 complex and plan to determine its structure. The proposed study will reveal the molecular mechanisms by which CED-4 facilitates the activation of CED-3.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 细胞凋亡在后生动物的发育和动态平衡中起着核心作用。细胞凋亡作为生长和分化的内在成分的基本意义直到最近十年才被认识到，细胞死亡途径首先在秀丽线虫中被发现，然后在智人中被发现。麻省理工学院的Bob Horvitz和他的同事负责分离和鉴定四个基因(EGL-1、Ced-9、Ced-4和Ced-3)，这些基因共同控制线虫细胞程序性死亡的开始。CED-3是杀伤细胞的半胱氨酸氨基转移酶，其激活需要CED-4。然而，CED-4如何促进CED-3的激活仍是完全未知的。我们最近发现CED-4形成一个八聚体凋亡体，它只招募CED-3单体的两个分子进行激活。被激活的CED-3仍然以全酶的形式与CED-4的凋亡体结合。我们已经结晶了CED-4-CED-3络合物，并计划确定其结构。这项拟议的研究将揭示CED-4促进CED-3激活的分子机制。