对氧化应激突变的阿塔克西亚 - 泰朗吉克塔西亚激活的结构性见解
Anna C Howes1, Olga Perisic1, Roger L Williams1
1MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
ATAXIA-telangiectasia突变 (ATM) 激酶通过二硫化键被氧化应激激活,导致结构变化,优化其催化活性. 这项研究揭示了由活性氧物种激活ATM的机制.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 突变的阿塔克西亚-泰朗吉克塔西亚 (ATM) 对于DNA损伤反应至关重要,由双链断裂激活.
- 通过活性氧物种 (ROS) 激活ATM的机制仍然不太清楚.
研究的目的:
- 阐明通过氧化应激激活ATM的结构基础.
- 为了解ROS如何触发ATM激酶活性提供见解.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定H2O2激活ATM的结构.
- 在氧化后的ATM形状变化的结构分析.
主要成果:
- 确定了H2O2激活ATM的冷-EM结构,揭示了分子内二硫化物桥梁.
- 在氧化ATM中观察到质体旋转和基质阻断PRD区域的释放.
- 确定了N-叶/C-叶扭曲,优化了催化,并使p53基质捕获成为可能.
结论:
- 氧化激活ATM涉及到特定的结构重组,包括二硫化物键形成和域重新定位.
- 这些结构变化提高了ATM的催化效率和基质结合.
- 提供了通过氧化应激激活ATM的第一个结构证据.
更多相关视频
09:33Imaging Approaches to Assessments of Toxicological Oxidative Stress Using Genetically-encoded Fluorogenic Sensors
Published on: February 7, 2018
10:24Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry
Published on: June 7, 2018
相关概念视频
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
DNA Damage can Stall the Cell Cycle
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Spontaneous and Induced Mutations
Electron Transport Chain: Complex III and IV
Radical Autoxidation
