Two different genes coding for fibronectin‐binding proteins from Streptococcus dysgalactiae

Abstract

The binding of Streptococcus dysgalactiae to fibronectin involves fibronetcin-binding protein(s) present on the bacterial surface. Previously, we reported the cloning of two different genes coding for cell-wall-associated fibronectin-binding proteins from S. dysgalactiae strain S2 [Lindgren, P.-E., Speziale, P., McGavin, M. J., Monstein, H.-J., Hook, M., Visai, L., Kostiainen, T., Bozzini, S. & Lindberg, M. (1992) J. Biol. Chem. 267, 1924-19311. The two genes, fibA and fnbB, have now been sequenced and the primary amino acid sequences of the two fibronectin-binding proteins, FnBA and FnBB, have been deduced. The two proteins have predicted molecular masses of 117 kDa and 122 kDa, respectively, and are organized in a similar way. The fibronectin-binding activities are localized in repeated motifs, 32-37 amino acids long, in the COOH-terminal regions of the proteins. The two fibronectin-binding proteins have heterologous amino acid sequences, except for the COOH-terminal ends which include the fibronectin-binding repeats. The fibronectin-binding regions of the genes have been fused to IgG-binding domains of protein A, utilizing the IgG-binding capacity of the resulting fusion proteins, to facilitate isolation of the fibronectin-binding domains.Fibronectin (Fn) is a large dimeric glycoprotein (molecular mass 430-470 kDa) which is found in plasma and other body fluids in a soluble form, and is incorporated as microfibrils into the extracellular matrix of most tissues as an insoluble form. The main function of Fn is presumably related to its ability to mediate the substrate adhesion of eucaryotic cells, which involves the binding of specific cell-surface receptors of the integrin family to certain domains in the Fn molecule. The first characterized binding site in Fn for eucaryotic cells contains the amino acid sequence RGD and is located in the central region of the protein (Pierschbacher and Ruoslahti, 1984). Recently, additional recognition sites have been identified (Komoriya et al., 1991). Fn also interacts with other matrix components ; binding sites for collagen, fibrin and sulfated glycosaminoglycans are located in discrete domains of the protein. The present knowledge of the structure and function of Fn has recently been summarized by Hynes (1990).

emm and sof gene sequence variation in relation to serological typing of opacity-factor-positive group A streptococci

“…With the exception of sof61, sof3875, sof1482, sof2967, sof1207, sof9 and sof44, for which protein sequences of 872-922 amino acids were deduced, the 62 different sof designations shown in Table 1 represent a remarkably variable set of related partial 190-470 residue Sof proteins that share 50-70 % sequence identity. The fnbA product from Streptococcus dysgalactiae (Lindgren et al, 1993) which also functions as an OF (Courtney et al, 1999), shared approximately 35-40 % sequence identity over this range (data not shown).…”

A Proline-Rich Region with a Highly Periodic Sequence in Streptococcal β Protein Adopts the Polyproline II Structure and Is Exposed on the Bacterial Surface

“…For example, such regions have been identified in the M6, SclA, and SclB proteins of Streptococcus pyogenes (20,37,38,49,50,58), in protein A of Staphylococcus aureus (18), in protein G of group G streptococci (15), in PspA and PspC of Streptococcus pneumoniae (6,13), in the P1 adhesin of Streptococcus mutans (12), in protein L of Peptostreptococcus magnus (26), and in FnBA of Streptococcus dysgalactiae (36). In all of these cases, the proline-rich region is located in the C-terminal, wall-proximal half of the protein.…”

High Affinity Streptococcal Binding to Human Fibronectin Requires Specific Recognition of Sequential F1 Modules

“…1C). FnBRs of S. aureus, S. pyogenes, and Streptococcus dysgalactiae bind to the N-terminal domain (NTD) of Fn (8,23,24), which is composed largely of a string of five F1 modules ( 1-5 F1). High resolution structures of subdomains of the NTD have been determined using nuclear magnetic resonance (NMR) spectroscopy (25)(26)(27).…”