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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 凋亡在后生动物的发展和稳态中起着核心作用。凋亡作为生长和分化的固有组成部分的基本意义仅在过去十年中才实现，在秀丽隐杆线虫（秀丽隐杆线虫）中首先发现了细胞死亡途径，然后在同性恋智者中发现了细胞死亡途径。鲍勃·霍维茨（Bob Horvitz）及其在麻省理工学院的同事负责四个基因（EGL-1，CED-9，CED-4和CED-3和CED-3）的隔离和表征，这些基因共同控制了秀丽隐杆线虫中编程细胞死亡的开始。 CED-3是杀细胞的caspase，其激活需要CED-4。但是，CED-4如何促进CED-3的激活仍然完全未知。我们最近表明，CED-4形成八重凋亡小体，该小体仅募集CED-3单体的两个分子进行激活。活化的CED-3保持与CED-4圆顶体为全酶。我们已经结晶了CED-4-CED-3复合物，并计划确定其结构。拟议的研究将揭示CED-4促进CED-3激活的分子机制。