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Solution structural model of the complex of the binding regions of human plasminogen with its M-protein receptor from Streptococcus pyogenes.


ABSTRACT: VEK50 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; R17H18) and a2- (RH2; R30H31) repeats within the A-domain of VEK50. Two mutant forms of VEK50, viz., VEK50[RH1/AA] (VEK50?RH1) and VEK50[RH2/AA] (VEK50?RH2), 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 13C- and 15N-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.

SUBMITTER: Yuan Y 

PROVIDER: S-EPMC6983471 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Solution structural model of the complex of the binding regions of human plasminogen with its M-protein receptor from Streptococcus pyogenes.

Yuan Yue Y   Ayinuola Yetunde A YA   Singh Damini D   Ayinuola Olawole O   Mayfield Jeffrey A JA   Quek Adam A   Whisstock James C JC   Law Ruby H P RHP   Lee Shaun W SW   Ploplis Victoria A VA   Castellino Francis J FJ  

Journal of structural biology 20190710 1


VEK50 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 (K2<sub>hPg</sub>), has been studied by high-resolution NMR spectroscopy. The data show that each VEK50 monomer in solution contains two tight binding sites for K2<sub>hPg</sub>, one each in the a1- (RH1; R<sup>17  ...[more]

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