Divergence in the plasminogen-binding group a streptococcal M protein family: functional conservation of binding site and potential role for immune selection of variants.
نویسندگان
چکیده
Group A streptococci (GAS) display receptors for the human zymogen plasminogen on the cell surface, one of which is the plasminogen-binding group A streptococcal M protein (PAM). Characterization of PAM genes from 12 GAS isolates showed significant variation within the plasminogen-binding repeat motifs (a1/a2) of this protein. To determine the impact of sequence variation on protein function, recombinant proteins representing five naturally occurring variants of PAM, together with a recombinant M1 protein, were expressed and purified. Equilibrium dissociation constants for the interaction of PAM variants with biotinylated Glu-plasminogen ranged from 1.58 to 4.99 nm. Effective concentrations of prototype PAM required for 50% inhibition of plasminogen binding to immobilized PAM variants ranged from 0.68 to 22.06 nm. These results suggest that although variation in the a1/a2 region of the PAM protein does affect the comparative affinity of PAM variants, the functional capacity to bind plasminogen is conserved. Additionally, a potential role for the a1 region of PAM in eliciting a protective immune response was investigated by using a mouse model for GAS infection. The a1 region of PAM was found to protect immunized mice challenged with a PAM-positive GAS strain. These data suggest a link between selective immune pressure against the plasminogen-binding repeats and the functional conservation of the binding domain in PAM variants.
منابع مشابه
In silico investigation of lactoferrin protein characterizations for the prediction of anti-microbial properties
Lactoferrin (Lf) is an iron-binding multi-functional glycoprotein which has numerous physiological functions such as iron transportation, anti-microbial activity and immune response. In this study, different in silico approaches were exploited to investigate Lf protein properties in a number of mammalian species. Results showed that the iron-binding site, DNA and RNA-binding sites, signal pepti...
متن کاملBiochemical characterization of PE_PGRS61 family protein of Mycobacterium tuberculosis H37Rv reveals the binding ability to fibronectin
Objective(s): The periodic binding of protein expressed by Mycobacterium tuberculosis H37Rv with the host cell receptor molecules i.e. fibronectin (Fn) is gaining significance because of its adhesive properties. The genome sequencing of M. tuberculosis H37Rv revealed that the proline-glutamic (PE) proteins contain polymorphic GC-rich repetitive sequences (PGRS) which have clinical importance i...
متن کاملPrediction of T-cell epitopes for designing a reverse vaccine against streptococcal bacteria
Streptococcal bacteria are among dangerous human pathogens with major prevalence worldwide. A good vaccine against streptococcal bacteria should have epitopes that confer protection from infection by different streptococcal bacteria types. we aimed was to recognize the most immunogenic and conserved epitopes of streptococcal bacteria, which could be a potential candidate for vaccine development...
متن کاملThe maintenance of high affinity plasminogen binding by group A streptococcal plasminogen-binding M-like protein is mediated by arginine and histidine residues within the a1 and a2 repeat domains.
Subversion of the plasminogen activation system is implicated in the virulence of group A streptococci (GAS). GAS displays receptors for the human zymogen plasminogen on the cell surface, one of which is the plasminogen-binding group A streptococcal M-like protein (PAM). The plasminogen binding domain of PAM is highly variable, and this variation has been linked to host selective immune pressur...
متن کاملMolecular Identification of Pre-Existing Immunityin Human against H9N2 Influenza Viruses Using HLA-A*0201 Binding Peptides
Background and Aims: The contribution genetic and antigenic diversity of H9N2 influenza viruses in evading from immune responses, cytotoxic T lymphocytes (CTL) epitopes in hemagglutinin (HA) protein restricted by HLA binding peptides was identified. Materials and Methods: Phylogenetic analyses were carried out for all of full length HA and deduced amino acid sequences of H9N2 viruses available ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 281 6 شماره
صفحات -
تاریخ انتشار 2006