Protein H — a surface protein of Streptococcus pyogenes with separate binding sites for lgG and albumin

Abstract

Protein H, a molecule expressed at the surface of some strains of Streptococcus pyogenes, has affinity for the constant (IgGFc) region of immunoglobulin (Ig) G. In absorption experiments with human plasma, protein H-sepharose could absorb not only IgG but also albumin from plasma. The affinity constant for the reaction between albumin and protein H was 7.8 x 10(9) M-1, which is higher than the affinity between IgG and protein H (Ka = 1.6 x 10(9) M-1). Fragments of protein H were generated with deletion plasmids and polymerase chain reaction (PCR) technology. Using these fragments in various protein-protein interaction assays, the binding of albumin was mapped to three repeats (C1-C3) in the C-terminal half of protein H. On the albumin molecule, the binding site for protein H was found to overlap the site for protein G, another albumin- and IgGFc-binding bacterial surface protein. Also IgGFc-binding could be mapped with the protein H fragments and the region was found N-terminally of the C repeats. A synthetic peptide (25 amino acid residues long) based on a sequence in this region was shown to inhibit the binding of protein H to immobilized IgG or IgGFc. This sequence was not found in previously described IgGFc-binding proteins. However, two other cell surface proteins of S. pyogenes exhibited highly homologous regions. The results identify IgGFc- and albumin-binding regions of protein H and further define and emphasize the convergent evolution among bacterial surface proteins interacting with human plasma proteins.

Function of the Fibronectin-Binding Serum Opacity Factor ofStreptococcus pyogenesin Adherence to Epithelial Cells

“…From the data shown in Table 1, it can be concluded that the association (K A ) and dissociation (K D ) constants are in the range of 10 7 and 10 Ϫ8 , respectively, which confirms a specific interaction of SOF75 with fibronectin. However, the binding strength is 1 order of magnitude lower, as described for other relevant MSCRAMMs of gram-positive cocci and their binding to human matrix proteins (2,14,21,28,37,49). It is possible that SOF is important for establishment of initial low-strength contact between the GAS and fibronectin, prior to high-affinity binding of SfbI or PrtF2 in SfbI-negative strains (28).…”

The GA module, a mobile albumin‐binding bacterial domain, adopts a three‐helix‐bundle structure

“…Like the GA modules the C repeats comprise about 40 amino acid residues, but these HSA-binding units show no sequence homology. Nevertheless, they compete for the same binding site in HSA [36]. These observations indicate that HSAbinding in Gram-positive bacteria has evolved convergently which, in turn, suggests that the ability of binding this abundant plasma protein adds selective advantages to the bacteria.…”

“…Similar binding properties do not imply structural similarity. For instance, the Igbinding domains of staphylococcal protein A and streptococcal protein G show no sequence homology and have very different global folds, but still bind to overlapping sites in IgG [36,37]. Neither does structural similarity imply similar binding characteristics.…”

“…Many members of the M protein family have homologous repeats located in the COOHterminal half of the molecule. These so-called C repeats have recently been found to bind HSA [36,43,44]. Whether or not the binding of HSA contributes to the antiphagocytic property is not known.…”

Purified Igg F C-Binding Proteins From M22 Group a Streptococcus Are Able to Induce Experimental Glomerulonephritis

“…Эффект повышения концен-трации IgG наблюдается и у пациентов с острыми стрептококковыми инфекциями. Помимо IgG, белки М семейства могут связывать и другие белки плазмы крови: фибронектин, фибриноген, плаз-миноген, альбумин, IgA и компоненты компле-мента [16,19,21]. Взаимодействие стрептококков с таким широким кругом белков крови не может пройти для организма-хозяина бесследно.…”