Structural basis underlying the synergism of NADase and SLO during group A Streptococcus infection

Wei Jiun Tsai, Yi Hsin Lai, Yong An Shi, Michal Hammel, Anthony P. Duff, Andrew E. Whitten, Karyn L. Wilde, Chun Ming Wu, Robert Knott, U. Ser Jeng, Chia Yu Kang, Chih Yu Hsu, Jian Li Wu, Pei Jane Tsai, Chuan Chiang-Ni, Jiunn Jong Wu, Yee Shin Lin, Ching Chuan Liu, Toshiya Senda, Shuying Wang

研究成果: Article同行評審

2 引文 斯高帕斯(Scopus)


Group A Streptococcus (GAS) is a strict human pathogen possessing a unique pathogenic trait that utilizes the cooperative activity of NAD+-glycohydrolase (NADase) and Streptolysin O (SLO) to enhance its virulence. How NADase interacts with SLO to synergistically promote GAS cytotoxicity and intracellular survival is a long-standing question. Here, the structure and dynamic nature of the NADase/SLO complex are elucidated by X-ray crystallography and small-angle scattering, illustrating atomic details of the complex interface and functionally relevant conformations. Structure-guided studies reveal a salt-bridge interaction between NADase and SLO is important to cytotoxicity and resistance to phagocytic killing during GAS infection. Furthermore, the biological significance of the NADase/SLO complex in GAS virulence is demonstrated in a murine infection model. Overall, this work delivers the structure-functional relationship of the NADase/SLO complex and pinpoints the key interacting residues that are central to the coordinated actions of NADase and SLO in the pathogenesis of GAS infection.

期刊Communications Biology
出版狀態Published - 2023 1月 31

All Science Journal Classification (ASJC) codes

  • 醫藥(雜項)
  • 一般生物化學,遺傳學和分子生物學
  • 一般農業與生物科學


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