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Article Dans Une Revue Journal of Biological Chemistry Année : 2017

Deciphering key residues involved in the virulence-promoting interactions between Streptococcus pneumoniae and human plasminogen

Résumé

Bacterial pathogens recruit circulating proteins to their own surfaces, coopting the host protein functions as a mechanism of virulence. Particular attention has focused on the binding of plasminogen (Plg) to bacterial surfaces, as it has been shown that this interaction contributes to bacterial adhesion to host cells, invasion of host tissues and evasion of the immune system. Several bacterial proteins are known to serve as receptors for Plg including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cytoplasmic enzyme that appears on the cell surface in this moonlighting role. Although Plg typically binds to these receptors via several lysine-binding domains, the specific interactions that occur have not been documented in all cases. However, identification of the relevant residues could help define strategies for mitigating the virulence of important human pathogens, like Streptococcus pneumoniae (Sp). To shed light on this question, we have described a combination of peptide-spot array screening, competition and SPR assays, high-resolution crystallography and mutational analyses to characterize the interaction between SpGAPDH and Plg. We identified three SpGAPDH lysire residues that were instrumental in defining the kinetic and thermodynamic parameters of the interaction. Altogether, the integration of the data presented in this work allows us to propose a structural model for the molecular interaction of the SpGAPDH-Plg complex.

Dates et versions

hal-01427824 , version 1 (06-01-2017)

Identifiants

Citer

Christophe J Moreau, Rémi Terrasse, Nicole M. Thielens, Thierry Vernet, Christine Gaboriaud, et al.. Deciphering key residues involved in the virulence-promoting interactions between Streptococcus pneumoniae and human plasminogen. Journal of Biological Chemistry, 2017, 292 (6), pp.2217-2225. ⟨10.1074/jbc.M116.764209⟩. ⟨hal-01427824⟩
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