7WVH

Structure of NAD+ glycohydrolase/Streptolysin O complex from Group A streptococcus

This is a non-PDB format compatible entry.

Summary for 7WVH

• Entry DOI: 10.2210/pdb7wvh/pdb
• Descriptor: NAD+-glycohydrolase, Streptolysin O (3 entities in total)
• Functional Keywords: group a streptococcus, toxins, protein complex, slo, nadase, toxin
• Biological source: Streptococcus pyogenes A20; More
• Total number of polymer chains: 4
• Total formula weight: 167454.20

Authors

Tsai, W.-J.,Wang, S.-Y. (deposition date: 2022-02-10, release date: 2023-02-15, Last modification date: 2023-11-29)

Primary citation

Tsai, W.J.,Lai, Y.H.,Shi, Y.A.,Hammel, M.,Duff, A.P.,Whitten, A.E.,Wilde, K.L.,Wu, C.M.,Knott, R.,Jeng, U.S.,Kang, C.Y.,Hsu, C.Y.,Wu, J.L.,Tsai, P.J.,Chiang-Ni, C.,Wu, J.J.,Lin, Y.S.,Liu, C.C.,Senda, T.,Wang, S.
Structural basis underlying the synergism of NADase and SLO during group A Streptococcus infection.
Commun Biol, 6:124-124, 2023

PubMed Abstract: 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.

PubMed: 36721030
DOI: 10.1038/s42003-023-04502-0

Experimental method

X-RAY DIFFRACTION (2.45 Å)