Structures of SdrD from Staphylococcus aureus reveal the molecular mechanism of how the cell surface receptors recognize their ligands

Wang, Xiao; Ge, Jingpeng; Liu, Bao; Hu, Yuanqi; Yang, Maojun

doi:10.1007/s13238-013-3009-x

Cited by 32 publications

(32 citation statements)

References 37 publications

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“…Molecular modeling revealed that the B repeats pack in a zig-zag fashion, suggesting that they could effectively provide the needed orientation and stability to present the A region away from the bacterial cell surface (9). For the S. aureus SdrD protein, which also contains the CnaB-like fold (36), it has been proposed that the B repeats could function as a spacer and a spring, helping to expose the adhesin (36). Our observations differ from the conclusions of an earlier study on purified proteins, suggesting that the structure, function, and folding of the ligand-binding A region are not affected by the presence of the B region and thus that the latter does not influence collagen binding (7).…”

Section: Discussionmentioning

confidence: 99%

Mechanical Strength and Inhibition of the Staphylococcus aureus Collagen-Binding Protein Cna

Herman‐Bausier

Valotteau

Pietrocola

et al. 2016

mBio

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The bacterial pathogen Staphylococcus aureus expresses a variety of cell surface adhesion proteins that bind to host extracellular matrix proteins. Among these, the collagen (Cn)-binding protein Cna plays important roles in bacterium-host adherence and in immune evasion. While it is well established that the A region of Cna mediates ligand binding, whether the repetitive B region has a dedicated function is not known. Here, we report the direct measurement of the mechanical strength of Cna-Cn bonds on living bacteria, and we quantify the antiadhesion activity of monoclonal antibodies (MAbs) targeting this interaction. We demonstrate that the strength of Cna-Cn bonds in vivo is very strong (~1.2 nN), consistent with the high-affinity “collagen hug” mechanism. The B region is required for strong ligand binding and has been found to function as a spring capable of sustaining high forces. This previously undescribed mechanical response of the B region is of biological significance as it provides a means to project the A region away from the bacterial surface and to maintain bacterial adhesion under conditions of high forces. We further quantified the antiadhesion activity of MAbs raised against the A region of Cna directly on living bacteria without the need for labeling or purification. Some MAbs are more efficient in blocking single-cell adhesion, suggesting that they act as competitive inhibitors that bind Cna residues directly involved in ligand binding. This report highlights the role of protein mechanics in activating the function of staphylococcal adhesion proteins and emphasizes the potential of antibodies to prevent staphylococcal adhesion and biofilm formation.

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Section: Discussionmentioning

confidence: 99%

Mechanical Strength and Inhibition of the Staphylococcus aureus Collagen-Binding Protein Cna

Herman‐Bausier

Valotteau

Pietrocola

et al. 2016

mBio

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“…The overall domain organization of Bbp/SdrE is similar to that of ClfA, except that there are three B repeats inserted between the A domain and SD repeat region (Josefsson et al, 1998a). These B repeats, which bind Ca 2+ , each adopt a β-sandwich fold and are thought to act as a spring-like linker connecting the A domain to the SD repeats (Josefsson et al, 1998b; Wang et al, 2013). Although Bbp was originally identified as a bone sialoprotein binding protein (Tung et al, 2000), it was later found to bind fibrinogen with high affinity (Vazquez et al, 2011).…”

Section: Fibrinogen/fibrin Mediated Clumpingmentioning

confidence: 99%

Staphylococcus aureus Aggregation and Coagulation Mechanisms, and Their Function in Host–Pathogen Interactions

Crosby

Kwieciński

Horswill

2016

Advances in Applied Microbiology

121

100

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The human commensal bacterium Staphylococcus aureus can cause a wide range of infections ranging from skin and soft tissue infections to invasive diseases like septicemia, endocarditis, and pneumonia. Muticellular organization almost certainly contributes to S. aureus pathogenesis mechanisms. While there has been considerable focus on biofilm formation and its role in colonizing prosthetic joints and indwelling devices, less attention has been paid to non-surface attached group behavior like aggregation and clumping. S. aureus is unique in its ability to coagulate blood, and it also produces multiple fibrinogen-binding proteins that facilitate clumping. Formation of clumps, which are large, tightly-packed groups of cells held together by fibrin(ogen), has been demonstrated to be important for S. aureus virulence and immune evasion. Clumps of cells are able to avoid detection by the host’s immune system due to a fibrin(ogen) coat that acts as a shield, and the size of the clumps facilitates evasion of phagocytosis. In addition, clumping could be an important early step in establishing infections that involve tight clusters of cells embedded in host matrix proteins, such as soft tissue abscesses and endocarditis. In this review we discuss clumping mechanisms and regulation, as well as what is known about how clumping contributes to immune evasion.

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“…All three chains have been shown to be critical for pathogenic adherence (Cheung et al 1991;Otto 2013). The crystal structure of several fibrinogen-binding MSCRAMMs have been solved so far, including ClfA (PDB ID 1N67) (Deivanayagam et al 2002), ClfB-Fg peptide complex (PDB ID 4F20) (Xiang et al 2012), SdrD (PDB ID 4JDZ) (Wang et al 2013a) from S. aureus, Srr-1 (PDB ID 4MBO) and Srr-2 (PDB ID 4MBR) (Seo et al 2013) from S. agalactiae, and SdrG (PDB ID 1R19 and 1R17, native and complex with fibrinopeptide, respectively) from Staphylococcus epidermidis (Ponnuraj et al 2003). When superposed, they share a highly conserved structural homology, but exhibit much less sequence identity (<20%) than that observed in collagen-binding MSCRAMMs.…”

Section: Fibrinogen-binding Mscrammsmentioning

confidence: 99%

“…Concerning the B-repetitive region in fibrinogenbinding MSCRAMMs, the crystal structure is available only for one B-repeat region of SdrD of S. aureus (Wang et al 2013a). This structure also contains the ligand-binding A-region (N2 and N3 domains), which precedes the B-repeat.…”

Section: Fibrinogen-binding Mscrammsmentioning

confidence: 99%

Isopeptide bond in collagen- and fibrinogen-binding MSCRAMMs

Sridharan

Ponnuraj

2016

Biophys Rev

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The internal isopeptide bonds are amide bonds formed autocatalytically between the side chains of Lys and Asn/Asp residues and have been discovered recently. These bonds are well conserved in Gram-positive bacterial pilin proteins and are also observed over a wide range of Gram-positive bacterial surface proteins. The presence of these bonds confers the pilus subunits with remarkable properties in terms of thermal stability and resistance to proteases. Like pili, microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) are also surface proteins found only in Gram-positive bacteria. They specifically interact with the extracellular matrix (ECM) molecules like collagen, fibrinogen, fibronectin, laminin, etc. Many biophysical and biochemical studies have been carried out to characterize the isopeptide bonds in pili proteins from Gram-positive bacteria, but no attempts have been made to study the isopeptide bonds in MSCRAMMs. This short review aims to study the significance of the isopeptide bonds in relation to their function, by analyzing the crystal structures of collagen- and fibrinogen-binding MSCRAMMs. In this analysis, interestingly, we observed that the putative isopeptide bonds are restricted to the collagen-binding MSCRAMMs. Based on analogy with bacterial pilus subunits, we hypothesize that the collagen-binding MSCRAMMs possessing putative isopeptide bonds exhibit similar structural properties, which could help the bacteria in colonizing the host and provide resistance against host-defense mechanisms.

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Structures of SdrD from Staphylococcus aureus reveal the molecular mechanism of how the cell surface receptors recognize their ligands

Abstract: Staphylococcus aureus is the most important

Cited by 32 publications

References 37 publications

Mechanical Strength and Inhibition of the Staphylococcus aureus Collagen-Binding Protein Cna

Mechanical Strength and Inhibition of the Staphylococcus aureus Collagen-Binding Protein Cna

Staphylococcus aureus Aggregation and Coagulation Mechanisms, and Their Function in Host–Pathogen Interactions

Isopeptide bond in collagen- and fibrinogen-binding MSCRAMMs

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