Streptavidin Promotes DNA Binding and Activation of cGAS to Enhance Innate Immunity

Yanqiong Zhang; Zhe Ma; Ying Wang; Joshua Boyer; Guoxin Ni; Liang Cheng; Siyuan Su; Zhigang Zhang; Zhichuan Zhu; Jiayi Qian; Lishan Su; Qi Zhang; Blossom Damania; Pengda Liu

iScience (Sep 2020)

Streptavidin Promotes DNA Binding and Activation of cGAS to Enhance Innate Immunity

Yanqiong Zhang,
Zhe Ma,
Ying Wang,
Joshua Boyer,
Guoxin Ni,
Liang Cheng,
Siyuan Su,
Zhigang Zhang,
Zhichuan Zhu,
Jiayi Qian,
Lishan Su,
Qi Zhang,
Blossom Damania,
Pengda Liu

Affiliations

Yanqiong Zhang: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Zhe Ma: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Ying Wang: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Joshua Boyer: Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Guoxin Ni: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Liang Cheng: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Siyuan Su: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Zhigang Zhang: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Zhichuan Zhu: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Jiayi Qian: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Lishan Su: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Qi Zhang: Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Blossom Damania: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; University of North Carolina Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Corresponding author
Pengda Liu: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Corresponding author

Journal volume & issue: Vol. 23, no. 9
p. 101463

Abstract

Read online

Summary: cGAS/STING signaling plays an essential role in sensing cytosolic DNA. cGAS activity is regulated by posttranslational modifications and binding partners. cGAS interactome largely includes mammalian or viral proteins. Whether and how bacterial proteins bind cGAS to modulate innate immunity remain elusive. Here, we found streptavidin, a secreted bacterial protein, selectively bound cGAS to promote DNA-induced cGAS activation and interferon-β production. Mechanistically, streptavidin enhanced DNA binding and cGAS phase separation, therefore facilitating cGAS activation. Using an HSV-1-infected mouse model, we found streptavidin nanoparticles facilitated HSV-1 clearance through improving innate immunity. Considering the clinical usage of streptavidin as an immune stimulant and drug delivery vehicle and its biotechnological usage for biotin-labeled protein purification and detection, our studies not only provide an example for a bacterial protein regulating cGAS activity but also suggest caution needs to be taken when using streptavidin in various applications given to its ability to induce innate immunity.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

About the journal

Abstract

Keywords