Activation of STING Based on Its Structural Features

Behzad Hussain; Yufeng Xie; Uzma Jabeen; Defen Lu; Bo Yang; Changxin Wu; Guijun Shang

doi:10.3389/fimmu.2022.808607

Activation of STING Based on Its Structural Features

Front Immunol. 2022 Jul 19:13:808607. doi: 10.3389/fimmu.2022.808607. eCollection 2022.

Authors

Behzad Hussain¹, Yufeng Xie², Uzma Jabeen³, Defen Lu⁴, Bo Yang^{5

6}, Changxin Wu¹, Guijun Shang^{5

6}

Affiliations

¹ The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, The Institutes of Biomedical Sciences, Shanxi University, Taiyuan, China.
² Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
³ Institute of Microbiology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
⁴ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁵ Shanxi Provincial Key Laboratory of Protein Structure Determination, Shanxi Academy of Advanced Research and Innovation, Taiyuan, China.
⁶ Shanxi Provincial Key Laboratory for Major Infectious Disease Response, Shanxi Academy of Advanced Research and Innovation, Taiyuan, China.

Abstract

The cGAS-cGAMP-STING pathway is an important innate immune signaling cascade responsible for the sensing of abnormal cytosolic double-stranded DNA (dsDNA), which is a hallmark of infection or cancers. Recently, tremendous progress has been made in the understanding of the STING activation mechanism from various aspects. In this review, the molecular mechanism of activation of STING protein based on its structural features is briefly discussed. The underlying molecular mechanism of STING activation will enable us to develop novel therapeutics to treat STING-associated diseases and understand how STING has evolved to eliminate infection and maintain immune homeostasis in innate immunity.

Keywords: cyclic GMP-AMP; cyclic GMP-AMP Synthase (cGAS); cyclic dinucleotide; innate immunity; stimulator of interferon genes.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Cytosol / metabolism
DNA
Immunity, Innate*
Membrane Proteins* / genetics
Signal Transduction

Substances

Membrane Proteins
DNA