6oq9
Solution structure of VEK50 in the bound form with plasminogen kringle 2
Structural highlights
FunctionPAM_STRPY Binds to human plasminogen (and plasmin) via its kringle repeats. Also binds to albumin, immunoglobulin G and fibrinogen. Could provide the bacteria with a mechanism for invasion, as streptococcal-bound plasmin could permit tissue penetration. Publication Abstract from PubMedVEK50 is a truncated peptide from a Streptococcal pyogenes surface human plasminogen (hPg) binding M-protein (PAM). VEK50 contains the full A-domain of PAM, which is responsible for its low nanomolar binding to hPg. The interaction of VEK50 with kringle 2, the PAM-binding domain in hPg (K2hPg), has been studied by high-resolution NMR spectroscopy. The data show that each VEK50 monomer in solution contains two tight binding sites for K2hPg, one each in the a1- (RH1; R(17)H(18)) and a2- (RH2; R(30)H(31)) repeats within the A-domain of VEK50. Two mutant forms of VEK50, viz., VEK50[RH1/AA] (VEK50(DeltaRH1)) and VEK50[RH2/AA] (VEK50(DeltaRH2)), were designed by replacing each RH with AA, thus eliminating one of the K2hPg binding sites within VEK50, and allowing separate study of each binding site. Using (13)C- and (15)N-labeled peptides, NMR-derived solution structures of VEK50 in its complex with K2hPg were solved. We conclude that the A-domain of PAM can accommodate two molecules of K2hPg docked within a short distance of each other, and the strength of the binding is slightly different for each site. The solution structure of the VEK50/K2hPg, complex, which is a reductionist model of the PAM/hPg complex, provides insights for the binding mechanism of PAM to a host protein, a process that is critical to S. pyogenes virulence. Solution structural model of the complex of the binding regions of human plasminogen with its M-protein receptor from Streptococcus pyogenes.,Yuan Y, Ayinuola YA, Singh D, Ayinuola O, Mayfield JA, Quek A, Whisstock JC, Law RHP, Lee SW, Ploplis VA, Castellino FJ J Struct Biol. 2019 Jul 10. pii: S1047-8477(19)30154-6. doi:, 10.1016/j.jsb.2019.07.005. PMID:31301349[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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