scholarly journals Cholix protein domain I functions as a carrier element for efficient apical to basal epithelial transcytosis

2020 ◽  
Vol 8 (1) ◽  
pp. 1710429 ◽  
Author(s):  
Alistair Taverner ◽  
Julia MacKay ◽  
Floriane Laurent ◽  
Tom Hunter ◽  
Keyi Liu ◽  
...  
Keyword(s):  
Protein Domain ◽  
Domain I ◽  
Carrier Element

scholarly journals Functional characterization and lineage analysis of broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics

2019 ◽  
Author(s):  
Natasha D. Durham ◽  
Aditi Agrawal ◽  
Eric Waltari ◽  
Derek Croote ◽  
Fabio Zanini ◽  
...  
Keyword(s):  
Dengue Virus ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Somatic Hypermutation ◽  
Functional Characterization ◽  
Vaccine Design ◽  
Protein Domain ◽  
Cell Repertoire ◽  
B Cell Repertoire ◽  
Domain I

AbstractEliciting broadly neutralizing antibodies (bNAbs) against the four dengue virus serotypes (DENV1-4) that are spreading into new territories is an important goal of vaccine design. To delineate bNAb targets, we characterized 28 monoclonal antibodies belonging to expanded and hypermutated clonal families identified by transcriptomic analysis of single plasmablasts from DENV-infected individuals. Among these, we identified two somatically related bNAbs that potently neutralized DENV1-4. Mutagenesis studies revealed that the major recognition determinants of these bNAbs are in E protein domain I, distinct from the only known class of human bNAbs against flaviviruses with a well-defined epitope. B cell repertoire analysis from acute-phase peripheral blood suggested a memory origin and divergent somatic hypermutation pathways for these bNAbs, and a limited number of mutations was sufficient for neutralizing activity. Our study suggests multiple B cell evolutionary pathways leading to DENV bNAbs targeting a novel epitope that can be exploited for vaccine design.

scholarly journals Dengue virus envelope protein domain I/II hinge determines long-lived serotype-specific dengue immunity

2014 ◽  
Vol 111 (5) ◽  
pp. 1939-1944 ◽  
Author(s):  
William B. Messer ◽  
Ruklanthi de Alwis ◽  
Boyd L. Yount ◽  
Scott R. Royal ◽  
Jeremy P. Huynh ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Envelope Protein ◽  
Protein Domain ◽  
Virus Envelope ◽  
Virus Envelope Protein ◽  
Domain I

Structural analysis of the interaction between urokinase-type plasminogen activator and its receptor: a potential target for anti-invasive cancer therapy

2002 ◽  
Vol 30 (2) ◽  
pp. 177-183 ◽  
Author(s):  
M. Ploug ◽  
H. Gårdsvoll ◽  
T. J. D. Jørgensen ◽  
L. Lønborg Hansen ◽  
K. Danø
Keyword(s):  
Cancer Cells ◽  
Plasminogen Activator ◽  
Chorioallantoic Membrane ◽  
Affinity Maturation ◽  
Protein Domain ◽  
Surrounding Tissue ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Protein Domain Family ◽  
Domain I

The ability to degrade the extracellular matrix by controlled proteolysis is an important property of malignant cancer cells, which enables them to invade the surrounding tissue and to gain access to the circulation by intravasation. One proteolytic system thought to be involved in these processes is urokinase-mediated plasminogen activation. Expression of a glycolipid-anchored receptor for urokinase-type plasminogen activator (uPA) targets this system to the cell surface. This receptor (uPAR) is composed of three homologous modules belonging to the Ly-6/uPAR/α-neurotoxin protein domain family. Integrity of the three-domain structure of uPAR is required for maintenance of its sub-nanomolar affinity for uPA, but the functional epitope for this interaction is primarily located in uPAR domain I. Using affinity maturation by combinatorial chemistry, we have recently identified a potent 9-mer peptide antagonist of the uPA-uPAR interaction having a high affinity for uPAR (Kd < 1 nM). Photoaffinity labelling suggests that this peptide interacts with a composite binding site in uPAR involving both domains I and III. When tested in a chicken chorioallantoic membrane assay that was developed to quantify intravasation of human cells, this antagonist was able to reduce the intravasation of HEp-3 cancer cells by approx. 60%.

scholarly journals Broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Natasha D Durham ◽  
Aditi Agrawal ◽  
Eric Waltari ◽  
Derek Croote ◽  
Fabio Zanini ◽  
...  
Keyword(s):  
Dengue Virus ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Somatic Hypermutation ◽  
Vaccine Design ◽  
Protein Domain ◽  
Cell Repertoire ◽  
B Cell Repertoire ◽  
Dengue Virus Serotypes ◽  
Domain I

Eliciting broadly neutralizing antibodies (bNAbs) against the four dengue virus serotypes (DENV1-4) that are spreading into new territories is an important goal of vaccine design. To define bNAb targets, we characterized 28 antibodies belonging to expanded and hypermutated clonal families identified by transcriptomic analysis of single plasmablasts from DENV-infected individuals. Among these, we identified J9 and J8, two somatically related bNAbs that potently neutralized DENV1-4. Mutagenesis studies showed that the major recognition determinants of these bNAbs are in E protein domain I, distinct from the only known class of human bNAbs against DENV with a well-defined epitope. B cell repertoire analysis from acute-phase peripheral blood suggested that J9 and J8 followed divergent somatic hypermutation pathways, and that a limited number of mutations was sufficient for neutralizing activity. Our study suggests multiple B cell evolutionary pathways leading to DENV bNAbs targeting a new epitope that can be exploited for vaccine design.

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