Molecular Interactions of Human Plasminogen with Fibronectin-binding Protein B (FnBPB), a Fibrinogen/Fibronectin-binding Protein from Staphylococcus aureus

Pietrocola, Giampiero; Nobile, Giulia; Gianotti, Valentina; Zapotoczna, Marta; Foster, Timothy J.; Geoghegan, Joan A.; Speziale, Pietro

doi:10.1074/jbc.m116.731125

Cited by 53 publications

(52 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To determine whether FnBPBs expressed by different strains of S. aureus also protected bacteria from the bactericidal effects of histones, the MBCs of H3 toward strains BH1CC (4), 8325-4 (42), and SH1000 (43) that express isoform I FnBPB and P1 (44) that expresses isoform IV FnBPB were very similar, although mutants lacking FnBPs (4,21,22,45) were ϳ3-fold more susceptible. This shows that both isoform I and isoform IV of FnBPB protect different strains of S. aureus to a similar degree despite isoform IV binding H3 less strongly than isoform I in vitro (Fig.…”

Section: Interactions Of Histones With S Aureus Fnbpbmentioning

confidence: 99%

“…We previously showed that FnBPs expressed on the surface of S. aureus can capture PLG, which can be activated by PLG activators to cleave FBG (22). Hence, we investigated whether recombinant FnBPB could simultaneously bind PLG and histone H3.…”

Section: Activated Plasminogen Captured By Fnbpb Cleaves H3 and Enhanmentioning

confidence: 99%

“…In the final latching step, the complex is stabilized by inserting the "latch" region in the N3 extension into the N2 subdomain through a ␤-strand complementation (18,19). The N2-N3 subdomains of both FnBPA and FnBPB each comprise seven distinct isoforms (14,20), also bind elastin (21) and plasminogen (PLG) (22), and promote biofilm formation by homophilic interactions (23). The C terminus of FnBPs comprises 10/11 tandemly repeated fibronectin-binding domains that bind type I modules of fibronectin by the tandem ␤-zipper mechanism (24,25).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Fibronectin-binding protein B (FnBPB) from Staphylococcus aureus protects against the antimicrobial activity of histones

Pietrocola

Nobile

Alfeo

et al. 2019

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Staphylococcus aureus is a Gram-positive bacterium that can cause both superficial and deep-seated infections. Histones released by neutrophils kill bacteria by binding to the bacterial cell surface and causing membrane damage. We postulated that cell wall-anchored proteins protect S. aureus from the bactericidal effects of histones by binding to and sequestering histones away from the cell envelope. Here, we focused on S. aureus strain LAC and by using an array of biochemical assays, including surface plasmon resonance and ELISA, discovered that fibronectin-binding protein B (FnBPB) is the main histone receptor. FnBPB bound all types of histones, but histone H3 displayed the highest affinity and bactericidal activity and was therefore investigated further. H3 bound specifically to the A domain of recombinant FnBPB with a K D of 86 nM, ϳ20-fold lower than that for fibrinogen. Binding apparently occurred by the same mechanism by which FnBPB binds to fibrinogen, because FnBPB variants defective in fibrinogen binding also did not bind H3. An FnBPB-deletion mutant of S. aureus LAC bound less H3 and was more susceptible to its bactericidal activity and to neutrophil extracellular traps, whereas an FnBPBoverexpressing mutant bound more H3 and was more resistant than the WT. FnBPB bound simultaneously to H3 and plasminogen, which after activation by tissue plasminogen activator cleaved the bound histone. We conclude that FnBPB provides a dual immune-evasion function that captures histones and prevents them from reaching the bacterial membrane and simultaneously binds plasminogen, thereby promoting its conversion to plasmin to destroy the bound histone. Staphylococcus aureus is a leading cause of diverse infections ranging from mild skin diseases such as impetigo, cellulitis, and skin abscesses to serious invasive diseases, including sepsis, endocarditis, osteomyelitis, toxic shock syndrome, and necro-tizing pneumoniae (1, 2). Strains that are resistant to multiple antibiotics are a major problem in healthcare settings in developed countries (3). These are referred to as hospital-associated methicillin-resistant S. aureus (MRSA) 3 and occur in individuals with pre-disposing risk factors, such as surgical wounds and indwelling medical devices (4, 5). Recently, there has been a dramatic increase in the incidence of community-associated MRSA infections that occur in otherwise healthy individuals (6, 7). Community-associated MRSA strains, exemplified by the USA300 clone (8), express a low level of resistance to ␤-lactam antibiotics and cause serious skin and soft tissue infections (9-11). S. aureus expresses a plethora of virulence factors, including both secreted and cell wall-anchored (CWA) proteins. The latter mediate adherence to the extracellular matrix, promote invasion of and survival within host cells, neutralize phagocytes, and modulate the immune response (12). CWA proteins are covalently anchored to peptidoglycan via a conserved C-terminal sorting signal mediated by the membrane-associated sortase A (13). Fibronec...

show abstract

Section: Interactions Of Histones With S Aureus Fnbpbmentioning

confidence: 99%

Section: Activated Plasminogen Captured By Fnbpb Cleaves H3 and Enhanmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Fibronectin-binding protein B (FnBPB) from Staphylococcus aureus protects against the antimicrobial activity of histones

Pietrocola

Nobile

Alfeo

et al. 2019

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently in an another study, A region of FnBP_B has been shown to bind to both plasminogen and fg, and the dual ligand binding is independent to one another. 44…”

Section: Search For Conserved Domains In Sequence Databasesmentioning

confidence: 99%

Sequence and structural analysis of fibronectin‐binding protein reveals importance of multiple intrinsic disordered tandem repeats

Saravanan

Ponnuraj

2018

J of Molecular Recognition

View full text Add to dashboard Cite

The location of certain amino acid sequences like repeats along the polypeptide chain is very important in the context of forming the overall shape of the protein molecule which in fact determines its function. In gram‐positive bacteria, fibronectin‐binding protein (FnBP) is one such repeat containing protein, and it is a cell wall‐attached protein responsible for various acute infections in human. Several studies on sequence, structure, and function of fibronectin‐binding regions of FnBPs were reported; however, no detailed study was carried out on the full‐length protein sequence. In the present study, we have made a thorough sequence and structure analysis on FnBP_A of Staphylococcus aureus and explored the presence of dual ligand‐binding ability of fibrinogen (fg)‐binding region and its molecular recognition processes. Multiple sequence alignment and protein‐protein docking analysis reveal the regions which are likely involved in dual ligand binding. Further analysis of docking of FnBP_A fg‐binding region and fn N‐terminal modules suggests that if the latter binds to the fg‐binding region of FnBP_A, it would inhibit the subsequent binding of fg because of steric hindrance. The sequence analysis further suggests that the abundance of disorder promoting residue glutamic acid and dual personality (both order/disorder promoting) residue threonine in tandem repeats of FnBP_A and B proteins possibly would help the molecule to undergo a conformational change while binding with fn by β‐zipper mechanism. The segment‐based power spectral analysis was carried out which helps to understand the distribution of hydrophobic residues along the sequence particularly in intrinsic disordered tandem repeats. The results presented here will help to understand the role of internal repeats and intrinsic disorder in the molecular recognition process of a pathogenic cell surface protein.

show abstract

“…MSCRAMMs usually have a multidomain organization and each domain can bind to a diverse array of host ligands. For example, the A domain of FnBPB (Fn-binding protein B) besides fibrinogen [14] recognizes and binds to elastin [15], plasminogen [16], and histones [16], while the C-terminal repetitive region interacts with Fn [17].…”

Section: Introductionmentioning

confidence: 99%

Fibronectin and Its Role in Human Infective Diseases

Speziale

Arciola

Pietrocola

2019

Cells

Self Cite

View full text Add to dashboard Cite

Fibronectin is a multidomain glycoprotein ubiquitously detected in extracellular fluids and matrices of a variety of animal and human tissues where it functions as a key link between matrices and cells. Fibronectin has also emerged as the target for a large number of microorganisms, particularly bacteria. There are clear indications that the binding of microorganism’ receptors to fibronectin promotes attachment to and infection of host cells. Each bacterium may use different receptors which recognize specific fibronectin domains, mostly the N-terminal domain and the central cell-binding domain. In many cases, fibronectin receptors have actions over and above that of simple adhesion: In fact, adhesion is often the prerequisite for invasion and internalization of microorganisms in the cells of colonized tissues. This review updates the current understanding of fibronectin receptors of several microorganisms with emphasis on their biochemical and structural properties and the role they can play in the onset and progression of host infection diseases. Furthermore, we describe the antigenic profile and discuss the possibility of designing adhesion inhibitors based on the structure of the fibronectin-binding site in the receptor or the receptor-binding site in fibronectin.

show abstract

Molecular Interactions of Human Plasminogen with Fibronectin-binding Protein B (FnBPB), a Fibrinogen/Fibronectin-binding Protein from Staphylococcus aureus

Cited by 53 publications

References 58 publications

Fibronectin-binding protein B (FnBPB) from Staphylococcus aureus protects against the antimicrobial activity of histones

Fibronectin-binding protein B (FnBPB) from Staphylococcus aureus protects against the antimicrobial activity of histones

Sequence and structural analysis of fibronectin‐binding protein reveals importance of multiple intrinsic disordered tandem repeats

Fibronectin and Its Role in Human Infective Diseases

Contact Info

Product

Resources

About