scholarly journals Structures of two fimbrial adhesins, AtfE and UcaD, from the uropathogenProteus mirabilis

2018 ◽  
Vol 74 (11) ◽  
pp. 1053-1062 ◽  
Author(s):  
Wangshu Jiang ◽  
Wimal Ubhayasekera ◽  
Melanie M. Pearson ◽  
Stefan D. Knight
Keyword(s):  
Receptor Binding ◽  
Biofilm Formation ◽  
Molecular Level ◽  
Sequence Similarity ◽  
Bacterial Pathogenesis ◽  
Cell Surfaces ◽  
Binding Domains ◽  
Fimbrial Adhesins ◽  
Tract Infections ◽  
Limited Sequence

The important uropathogenProteus mirabilisencodes a record number of chaperone/usher-pathway adhesive fimbriae. Such fimbriae, which are used for adhesion to cell surfaces/tissues and for biofilm formation, are typically important virulence factors in bacterial pathogenesis. Here, the structures of the receptor-binding domains of the tip-located two-domain adhesins UcaD (1.5 Å resolution) and AtfE (1.58 Å resolution) from twoP. mirabilisfimbriae (UCA/NAF and ATF) are presented. The structures of UcaD and AtfE are both similar to the F17G type of tip-located fimbrial receptor-binding domains, and the structures are very similar despite having only limited sequence similarity. These structures represent an important step towards a molecular-level understanding ofP. mirabilisfimbrial adhesins and their roles in the complex pathogenesis of urinary-tract infections.

scholarly journals Predicting bacteriophage hosts based on sequences of annotated receptor-binding proteins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dimitri Boeckaerts ◽  
Michiel Stock ◽  
Bjorn Criel ◽  
Hans Gerstmans ◽  
Bernard De Baets ◽  
...  
Keyword(s):  
Machine Learning ◽  
Predictive Model ◽  
Receptor Binding ◽  
Bacterial Infections ◽  
Sequence Data ◽  
Sequence Similarity ◽  
Area Under The Curve ◽  
Local Alignment ◽  
Search Tool ◽  
Different Levels

AbstractNowadays, bacteriophages are increasingly considered as an alternative treatment for a variety of bacterial infections in cases where classical antibiotics have become ineffective. However, characterizing the host specificity of phages remains a labor- and time-intensive process. In order to alleviate this burden, we have developed a new machine-learning-based pipeline to predict bacteriophage hosts based on annotated receptor-binding protein (RBP) sequence data. We focus on predicting bacterial hosts from the ESKAPE group, Escherichia coli, Salmonella enterica and Clostridium difficile. We compare the performance of our predictive model with that of the widely used Basic Local Alignment Search Tool (BLAST). Our best-performing predictive model reaches Precision-Recall Area Under the Curve (PR-AUC) scores between 73.6 and 93.8% for different levels of sequence similarity in the collected data. Our model reaches a performance comparable to that of BLASTp when sequence similarity in the data is high and starts outperforming BLASTp when sequence similarity drops below 75%. Therefore, our machine learning methods can be especially useful in settings in which sequence similarity to other known sequences is low. Predicting the hosts of novel metagenomic RBP sequences could extend our toolbox to tune the host spectrum of phages or phage tail-like bacteriocins by swapping RBPs.

scholarly journals Pseudomonas aeruginosa uses multiple receptors for adherence to laminin during infection of the respiratory tract and skin wounds

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Magnus Paulsson ◽  
Yu-Ching Su ◽  
Tamara Ringwood ◽  
Fabian Uddén ◽  
Kristian Riesbeck
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Outer Membrane ◽  
Heparin Binding ◽  
Surface Receptors ◽  
Binding Domains ◽  
Laminin Receptors ◽  
Multiple Receptors ◽  
Main Component ◽  
Tract Infections

AbstractPseudomonas aeruginosa efficiently adheres to human tissues, including the lungs and skin, causing infections that are difficult to treat. Laminin is a main component of the extracellular matrix, and in this study we defined bacterial laminin receptors on P. aeruginosa. Persistent clinical P. aeruginosa isolates from patients with cystic fibrosis, wounds or catheter-related urinary tract infections bound more laminin compared to blood isolates. Laminin receptors in the outer membrane were revealed by 2D-immunblotting, and the specificities of interactions were confirmed with ELISA and biolayer interferometry. Four new high-affinity laminin receptors were identified in the outer membrane; EstA, OprD, OprG and PA3923. Mutated bacteria devoid of these receptors adhered poorly to immobilized laminin. All bacterial receptors bound to the heparin-binding domains on LG4 and LG5 of the laminin alpha chain as assessed with truncated laminin fragments, transmission electron microscopy and inhibition by heparin. In conclusion, P. aeruginosa binds laminin via multiple surface receptors, and isolates from lungs of cystic fibrosis patients bound significantly more laminin compared to bacteria isolated from the skin and urine. Since laminin is abundant in both the lungs and skin, we suggest that laminin binding is an important mechanism in P. aeruginosa pathogenesis.

scholarly journals Dissociation of Heparan Sulfate and Receptor Binding Domains of Hepatocyte Growth Factor Reveals That Heparan Sulfate-c-Met Interaction Facilitates Signaling

2001 ◽  
Vol 276 (35) ◽  
pp. 32977-32983 ◽  
Author(s):  
Jeffrey S. Rubin ◽  
Regina M. Day ◽  
Diane Breckenridge ◽  
Nese Atabey ◽  
William G. Taylor ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Heparan Sulfate ◽  
Receptor Binding ◽  
Binding Domains ◽  
Hepatocyte Growth

scholarly journals The Gammaherpesvirus Chemokine Binding Protein Binds to the N Terminus of CXCL8

2003 ◽  
Vol 77 (15) ◽  
pp. 8588-8592 ◽  
Author(s):  
Louise M. C. Webb ◽  
Ian Clark-Lewis ◽  
Antonio Alcami
Keyword(s):  
Receptor Binding ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Binding Protein ◽  
Sequence Similarity ◽  
Structural Requirements ◽  
Murine Gammaherpesvirus ◽  
N Terminus ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

ABSTRACT Viruses encode proteins that disrupt chemokine responses. The murine gammaherpesvirus 68 gene M3 encodes a chemokine binding protein (vCKBP-3) which has no sequence similarity to chemokine receptors but inhibits chemokine receptor binding and activity. We have used a panel of CXCL8 analogs to identify the structural requirements for CXCL8 to bind to vCKBP-3 in a scintillation proximity assay. Our data suggest that vCKBP-3 acts by mimicking the binding of chemokine receptors to CXCL8.

scholarly journals The hormone neuroparsin seems essential in Lepidoptera but not in domesticated silkworms

2019 ◽  
Author(s):  
Jan A. Veenstra
Keyword(s):  
Bombyx Mori ◽  
Genome Assembly ◽  
Galleria Mellonella ◽  
Sequence Similarity ◽  
Neuroendocrine Cells ◽  
Primary Sequence ◽  
Genome Assemblies ◽  
Limited Sequence ◽  
Wax Moth

AbstractThe primary sequence of the Arthropod neurohormone neuroparsin is so variable that so far no orthologs from moths and butterflies have been characterized, even though classical neurosecretory stains identify cells that are homologous to those producing this hormone in other insect species. Here Lepidopteran cDNAs showing limited sequence similarity to other insect neuroparsins are described. That these cDNAs do indeed code for authentic neuroparsins was confirmed by in situ hybridization in the wax moth, Galleria mellonella, which labeled the neuroparsin neuroendocrine cells. Although in virtually all genome assemblies from Lepidoptera a neuroparsin gene could be identified, the genome assembly from the silkworm, Bombyx mori, has a neuroparsin gene containing a 16 nucleotide deletion that renders this gene nonfunctional. Although only a small number of all silkworm strains carry this deletion, it suggests that the domestication of the silkworm has rendered the function of this neurohormone dispensable.

scholarly journals Broad cross-reactivity across sarbecoviruses exhibited by a subset of COVID-19 donor-derived neutralizing antibodies

2021 ◽  
Author(s):  
Claudia A. Jette ◽  
Alexander A. Cohen ◽  
Priyanthi N.P. Gnanapragasam ◽  
Frauke Muecksch ◽  
Yu E. Lee ◽  
...  
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Cross Reactivity ◽  
Antibody Therapeutics ◽  
Binding Domains ◽  
Cryptic Epitope ◽  
Binding Antibody ◽  
Β Sheet ◽  
Potent Neutralization

SummaryMany anti-SARS-CoV-2 neutralizing antibodies target the ACE2-binding site on viral spike receptor-binding domains (RBDs). The most potent antibodies recognize exposed variable epitopes, often rendering them ineffective against other sarbecoviruses and SARS-CoV-2 variants. Class 4 anti-RBD antibodies against a less-exposed, but more-conserved, cryptic epitope could recognize newly-emergent zoonotic sarbecoviruses and variants, but usually show only weak neutralization potencies. We characterized two class 4 anti-RBD antibodies derived from COVID-19 donors that exhibited broad recognition and potent neutralization of zoonotic coronavirus and SARS-CoV-2 variants. C118-RBD and C022-RBD structures revealed CDRH3 mainchain H-bond interactions that extended an RBD β-sheet, thus reducing sensitivity to RBD sidechain changes, and epitopes that extended from the cryptic epitope to occlude ACE2 binding. A C118-spike trimer structure revealed rotated RBDs to allow cryptic epitope access and the potential for intra-spike crosslinking to increase avidity. These studies facilitate vaccine design and illustrate potential advantages of class 4 RBD-binding antibody therapeutics.

scholarly journals Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein

2020 ◽  
Author(s):  
Alexandra C. Walls ◽  
Young-Jun Park ◽  
M. Alexandra Tortorici ◽  
Abigail Wall ◽  
Andrew T. McGuire ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Target Cells ◽  
Furin Cleavage ◽  
Humoral Immune ◽  
Binding Domains ◽  
Furin Cleavage Site ◽  
Recent Emergence ◽  
Novel Coronavirus

SUMMARYThe recent emergence of a novel coronavirus associated with an ongoing outbreak of pneumonia (Covid-2019) resulted in infections of more than 72,000 people and claimed over 1,800 lives. Coronavirus spike (S) glycoprotein trimers promote entry into cells and are the main target of the humoral immune response. We show here that SARS-CoV-2 S mediates entry in VeroE6 cells and in BHK cells transiently transfected with human ACE2, establishing ACE2 as a functional receptor for this novel coronavirus. We further demonstrate that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, which correlates with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and other SARS-related CoVs. We determined a cryo-electron microscopy structure of the SARS-CoV-2 S ectodomain trimer, demonstrating spontaneous opening of the receptor-binding domain, and providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal sera potently inhibited SARS-CoV-2 S-mediated entry into target cells, thereby indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

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