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Capture Compound Mass Spectrometry - A Powerful Tool to Identify Novel c-di-GMP Effector Proteins
Published on: March 29, 2015
Ku proteins promote DNA binding and condensation of cyclic GMP-AMP synthase
Xinyue Tao1, Jiali Song2, Ying Song2
1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Jia #3 Datun Road, Chaoyang District, Beijing 100101, China; Institute of Stem Cells and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
Abstract:
Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that plays a critical role in regulating antiviral signaling. cGAS binds to DNA and catalyzes the synthesis of cyclic GMP-AMP (cGAMP), which is essential for downstream signal transduction. The antiviral response is a rapid biological process; however, cGAS itself has relatively low DNA binding affinity, implying that formation of the cGAS-DNA complex requires an additional factor(s) that promotes cGAS-DNA binding, allowing efficient antiviral signal transduction. Here, we report that the Ku proteins (Ku80 and Ku70) directly interact with cGAS and positively regulate cGAS-mediated antiviral signaling. Mechanistically, we find that the interaction of the Ku proteins with cGAS significantly increases the DNA-binding affinity of cGAS and promotes cGAS condensation in the cytosol, thereby enhancing cGAS catalytic activity. Our results show that the Ku proteins are critical partners of cGAS in sensing DNA virus infection and ensuring efficient innate immune signal transduction.
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