6BZK

Solution structure of KTI55

Summary for 6BZK

• Entry DOI: 10.2210/pdb6bzk/pdb
• NMR Information: BMRB: 30390
• Descriptor: M protein (1 entity in total)
• Functional Keywords: plasminogen binding peptide, protein binding
• Biological source: Streptococcus pyogenes
• Total number of polymer chains: 1
• Total formula weight: 6799.46

Authors

Castellino, F.J.,Qiu, C.,Yuan, Y. (deposition date: 2017-12-24, release date: 2019-01-16, Last modification date: 2024-05-01)

Primary citation

Qiu, C.,Yuan, Y.,Zajicek, J.,Liang, Z.,Balsara, R.D.,Brito-Robionson, T.,Lee, S.W.,Ploplis, V.A.,Castellino, F.J.
Contributions of different modules of the plasminogen-binding Streptococcus pyogenes M-protein that mediate its functional dimerization.
J.Struct.Biol., 204:151-164, 2018

PubMed Abstract: Group A Streptococcus pyogenes (GAS) is a causative agent of pharyngeal and dermal infections in humans. A major virulence determinant of GAS is its dimeric signature fibrillar M-protein (M-Prt), which is evolutionarily designed in modules, ranging from a hypervariable extracellular N-terminal region to a progressively more highly conserved C-terminus that is covalently anchored to the cell wall. Of the >250 GAS isolates classified, only the subset of skin-trophic Pattern D strains expresses a specific serotype of M-Prt, PAM, that directly binds to host human plasminogen (hPg) via its extracellular NH-terminal variable A-domain region. This interaction allows these GAS strains to accumulate components of the host fibrinolytic system on their surfaces to serve extracellular functions. While structure-function studies have been accomplished on M-Prts from Pattern A-C GAS isolates with different direct ligand binding properties compared to PAM, much less is known regarding the structure-function relationships of PAM-type M-Prts, particularly their dimerization determinants. To examine these questions, PAMs from seven GAS strains with sequence variations in the NH-terminal ligand binding domains, as well as truncated versions of PAM, were designed and studied. The results from bioinformatic and biophysical analyses show that the different domains of PAM are disparately engaged in dimerization. From these data, we propose an experimentally-based model for PAM secondary and quaternary structures that is highly dependent on the conserved helical C-terminal C-D-domains. In addition, while the N-terminal regions of PAMs are variable in sequence, the binding properties of hPg and its activated product, plasmin, to the A-domain, remain intact.

PubMed: 30071314
DOI: 10.1016/j.jsb.2018.07.017

Experimental method

SOLUTION NMR