scholarly journals Fibronectin and Its Role in Human Infective Diseases

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1516 ◽  
Author(s):  
Pietro Speziale ◽  
Carla Renata Arciola ◽  
Giampiero Pietrocola
Keyword(s):  
Binding Site ◽  
Host Cells ◽  
Cell Binding ◽  
Receptor Binding Site ◽  
Number Of Microorganisms ◽  
Fibronectin Binding ◽  
Fibronectin Domains ◽  
Host Infection ◽  
Antigenic Profile ◽  
Cell Binding Domain

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.

scholarly journals Fibronectin mediates Treponema pallidum cytadherence through recognition of fibronectin cell-binding domain.

1985 ◽  
Vol 161 (3) ◽  
pp. 514-525 ◽  
Author(s):  
D D Thomas ◽  
J B Baseman ◽  
J F Alderete
Keyword(s):  
Treponema Pallidum ◽  
Binding Domain ◽  
Host Cells ◽  
Scatchard Analysis ◽  
Cell Surfaces ◽  
Cell Binding ◽  
High Affinity ◽  
Fibronectin Binding ◽  
Affinity Interaction ◽  
Cell Binding Domain

The specificity of the interaction between Treponema pallidum and fibronectin was demonstrated. Treatment of host cells with only antifibronectin sera and not anticollagen or antilaminin sera, inhibited treponemal cytadsorption. Incubation of fibronectin-coated coverslips with monoclonal antibody to the cell-binding domain of fibronectin reduced treponemal attachment to the same extent as antifibronectin serum. Both iodinated fibronectin and iodinated cell-binding domain bound to T. pallidum in a saturable manner. Specificity of the T. pallidum association with the cell-binding domain was the most effective inhibitor of the binding of either radioiodinated cell-binding domain or fibronectin to T. pallidum. Scatchard analysis gave Kd on the order of 10(-7) M for both cell-binding domain and fibronectin binding to T. pallidum, consistent with the high affinity interaction of these organisms with host cell surfaces. Finally, the same level of attachment of treponemes was achieved on coverslips coated with cell-binding domain as that observed for organisms incubated with fibronectin, indicating that the cell-binding domain polypeptide is functionally identical to fibronectin in mediating T. pallidum adherence.

scholarly journals A novel fibronectin binding site required for fibronectin fibril growth during matrix assembly

2001 ◽  
Vol 154 (5) ◽  
pp. 1081-1088 ◽  
Author(s):  
Jan L. Sechler ◽  
Hongwei Rao ◽  
Anne Marie Cumiskey ◽  
Irbert Vega-Colón ◽  
Michael S. Smith ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Binding Site ◽  
Large Deletion ◽  
Specific Function ◽  
Binding Assays ◽  
Cell Binding ◽  
Matrix Assembly ◽  
Type Iii ◽  
Fibronectin Binding ◽  
Cell Binding Domain

Fibronectin (FN) assembly into a fibrillar extracellular matrix is a stepwise process requiring participation from multiple FN domains. Fibril formation is regulated in part by segments within the first seven type III repeats (III1–7). To define the specific function(s) of this region, recombinant FNs (recFNs) containing an overlapping set of deletions were tested for the ability to assemble into fibrils. Surprisingly, recFN lacking type III repeat III1 (FNΔIII1), which contains a cryptic FN binding site and has been suggested to be essential for fibril assembly, formed a matrix identical in all respects to a native FN matrix. Similarly, displacement of the cell binding domain in repeats III9–10 to a position close to the NH2-terminal assembly domain, as well as a large deletion spanning repeats III4–7, had no effect on assembly. In contrast, two deletions that included repeat III2, ΔIII1–2 and ΔIII2–5, caused significant reductions in fibril elongation, although binding of FN to the cell surface and initiation of assembly still proceeded. Using individual repeats in binding assays, we show that III2 but not III1 contains an FN binding site. Thus, these results pinpoint repeat III2 as an important module for FN–FN interactions during fibril growth.

scholarly journals Binding to Human Extracellular Matrix byNeisseria meningitidis

1998 ◽  
Vol 66 (4) ◽  
pp. 1791-1794 ◽  
Author(s):  
Thomas Eberhard ◽  
Ritva Virkola ◽  
Timo Korhonen ◽  
Göran Kronvall ◽  
Måns Ullberg
Keyword(s):  
Extracellular Matrix ◽  
Neisseria Meningitidis ◽  
Binding Site ◽  
Binding Domain ◽  
Cell Binding ◽  
Matrix Components ◽  
Cell Binding Domain ◽  
Healthy Carriers ◽  
Better Than

ABSTRACT Adhesion of Neisseria meningitidis strains to extracellular matrix (ECM) and purified matrix components was examined. Most strains bound to subendothelial ECM as well as to immobilized fibronectin and types I, III, and V collagen. Strains from healthy carriers adhered significantly better than isolates from patients. The binding site was localized to the central 75-kDa cell-binding domain of the fibronectin molecule. This domain has not been described previously to interact with bacterial structures.

scholarly journals The Primed Ebolavirus Glycoprotein (19-Kilodalton GP1,2): Sequence and Residues Critical for Host Cell Binding

2009 ◽  
Vol 83 (7) ◽  
pp. 2883-2891 ◽  
Author(s):  
Derek Dube ◽  
Matthew B. Brecher ◽  
Sue E. Delos ◽  
Sean C. Rose ◽  
Edward W. Park ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Disulfide Bonds ◽  
Mutational Analysis ◽  
Small Region ◽  
Host Cells ◽  
High Yield ◽  
Cell Binding ◽  
Receptor Binding Site ◽  
Critical Binding ◽  
Β Sheet

ABSTRACT Entry of ebolavirus (EBOV) into cells is mediated by its glycoprotein (GP1,2), a class I fusion protein whose structure was recently determined (J. E. Lee et al., Nature 454:177-182, 2008). Here we confirmed two major predictions of the structural analysis, namely, the residues in GP1 and GP2 that remain after GP1,2 is proteolytically primed by endosomal cathepsins for fusion and residues in GP1 that are critical for binding to host cells. Mass spectroscopic analysis indicated that primed GP1,2 contains residues 33 to 190 of GP1 and all residues of GP2. The location of the receptor binding site was determined by a two-pronged approach. We identified a small receptor binding region (RBR), residues 90 to 149 of GP1, by comparing the cell binding abilities of four RBR proteins produced in high yield. We characterized the binding properties of the optimal RBR (containing GP1 residues 57 to 149) and then conducted a mutational analysis to identify critical binding residues. Substitutions at four lysines (K95, K114, K115, and K140) decreased binding and the ability of RBR proteins to inhibit GP1,2-mediated infection. K114, K115, and K140 lie in a small region modeled to be located on the top surface of the chalice following proteolytic priming; K95 lies deeper in the chalice bowl. Combined with those of Lee et al., our findings provide structural insight into how GP1,2 is primed for fusion and define the core of the EBOV RBR (residues 90 to 149 of GP1) as a highly conserved region containing a two-stranded β-sheet, the two intra-GP1 disulfide bonds, and four critical Lys residues.

scholarly journals Fibronectin tetrapeptide is target for syphilis spirochete cytadherence.

1985 ◽  
Vol 162 (5) ◽  
pp. 1715-1719 ◽  
Author(s):  
D D Thomas ◽  
J B Baseman ◽  
J F Alderete
Keyword(s):  
Amino Acid ◽  
Active Site ◽  
Treponema Pallidum ◽  
Eukaryotic Cell ◽  
Binding Domain ◽  
Host Cells ◽  
Cell Binding ◽  
Cell Monolayers ◽  
Cell Binding Domain ◽  
Domain Acquisition

The syphilis bacterium, Treponema pallidum, parasitizes host cells through recognition of fibronectin (Fn) on cell surfaces. The active site of the Fn molecule has been identified as a four-amino acid sequence, arg-gly-asp-ser (RGDS), located on each monomer of the cell-binding domain. The synthetic heptapeptide gly-arg-gly-asp-ser-pro-cys (GRGDSPC), with the active site sequence RGDS, specifically competed with 125I-labeled cell-binding domain acquisition by T. pallidum. Additionally, the same heptapeptide with the RGDS sequence diminished treponemal attachment to HEp-2 and HT1080 cell monolayers. Related heptapeptides altered in one key amino acid within the RGDS sequence failed to inhibit Fn cell-binding domain acquisition or parasitism of host cells by T. pallidum. The data support the view that T. pallidum cytadherence of host cells is through recognition of the RGDS sequence also important for eukaryotic cell-Fn binding.

Mutations in the SARS CoV-2 spike protein may cause functional changes in the protein quaternary structure

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ekrem Akbulut
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Quaternary Structure ◽  
Host Cells ◽  
Functional Structure ◽  
Sequence Information ◽  
Receptor Binding Site ◽  
Functional Changes ◽  
Severity Of Disease ◽  
Genome Sequence Information

Abstract Objectives This study aimed to model the changes resulting from mutations in surface (spike/S) glycoproteins, which play a key role in the entry of the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) into host cells, in a protein quaternary structure and to evaluate their possible effects on the functional structure. Methods Genome sequence information of SARS CoV-2-infected patients located in Turkey was obtained from the GISAID EpiCoV database. Structural analysis of spike proteins was done using bioinformatics tools (MAFFT, PSIPRED, ProMod3, PyMoL and DynOmics). Results We identified 76 Thr>Ile mutations in the N-terminal domain; 468 Ile>Val mutations in the receptor binding site and 614 Asp>Gly, 679 Asn>Lys, 771 Ala>Val and 772 Val>Ile mutations in the S1 subunit. It has been observed that the mutations, except those of residues 771 and 772, may cause significant conformational, topological and electrostatic changes in a protein quaternary structure. It has been determined that the mutations in the receptor binding site transform the protein structure into a formation that can mask the binding site and affect receptor affinity. Conclusions It has been considered that SARS CoV-2 S glycoprotein mutations may cause changes in a protein functional structure that can affect the severity of disease.

In vivoinfection byTrypanosoma cruzi: The conserved FLY domain of the gp85/trans-sialidase family potentiates host infection

Parasitology ◽  
2010 ◽  
Vol 138 (4) ◽  
pp. 481-492 ◽  
Author(s):  
R. R. TONELLI ◽  
A. C. TORRECILHAS ◽  
J. F. JACYSYN ◽  
M. A. JULIANO ◽  
W. COLLI ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Pathological Condition ◽  
Protozoan Parasite ◽  
Treg Cells ◽  
Relative Increase ◽  
Host Cells ◽  
Cell Binding ◽  
Host Infection ◽  
Binding Sequence

SUMMARYTrypanosoma cruziis a protozoan parasite that infects vertebrates, causing in humans a pathological condition known as Chagas’ disease. The infection of host cells byT. cruziinvolves a vast collection of molecules, including a family of 85 kDa GPI-anchored glycoproteins belonging to the gp85/trans-sialidase superfamily, which contains a conserved cell-binding sequence (VTVXNVFLYNR) known as FLY, for short. Herein, it is shown that BALB/c mice administered with a single dose (1μg/animal, intraperitoneally) of FLY-synthetic peptide are more susceptible to infection byT. cruzi, with increased systemic parasitaemia (2-fold) and mortality. Higher tissue parasitism was observed in bladder (7·6-fold), heart (3-fold) and small intestine (3·6-fold). Moreover, an intense inflammatory response and increment of CD4+T cells (1·7-fold) were detected in the heart of FLY-primed and infected animals, with a 5-fold relative increase of CD4+CD25+FoxP3+T (Treg) cells. Mice treated with anti-CD25 antibodies prior to infection, showed a decrease in parasitaemia in the FLY model employed. In conclusion, the results suggest that FLY facilitatesin vivoinfection byT. cruziand concurs with other factors to improve parasite survival to such an extent that might influence the progression of pathology in Chagas’ disease.

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