Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

Microbiology ◽  
2003 ◽  
Vol 149 (7) ◽  
pp. 1849-1858 ◽  
Author(s):  
Emily A. L. Thompson ◽  
Ian M. Feavers ◽  
Martin C. J. Maiden
Keyword(s):  
Nucleotide Substitution ◽  
Protein Sequences ◽  
Variable Region ◽  
Peptide Sequence ◽  
Immunodominant Epitope ◽  
Nomenclature System ◽  
Amino Terminal ◽  
Vaccine Component ◽  
Amino Terminal Domain ◽  
Cell Elisa

Meningococcal FetA (FrpB), an iron-regulated outer-membrane protein and vaccine component, was shown to be highly diverse: a total of 60 fetA alleles, encoding 56 protein sequences, were identified from 107 representative Neisseria meningitidis isolates. Phylogenetic analysis established that the allelic variants had been generated by both point mutation and horizontal genetic exchange. Nucleotide substitution was unevenly distributed in the gene, which contained both conserved and variable sequence regions. The most conserved region of the translated peptide sequence corresponded to an amino-terminal domain of the protein and the most diverse region to a previously identified variable region (VR). A nomenclature system for the peptides encoded by the VR was devised which classified 24 variants into 5 FetA variant families. On the basis of these data, murine polyclonal sera specific for four FetA variants were generated. The reactivities of these sera in whole-cell ELISA experiments were consistent with the hypothesis that the VR encoded an immunodominant epitope and indicated that the sera reacted mainly with variants against which they were raised. The diversity of this protein is likely to limit its effectiveness as a vaccine component.

Characterization of a Mode of Specific Binding of Fibrin Monomer through its Amino-Terminal Domain by Macrophages and Macrophage Cell-Lines

1990 ◽  
Vol 63 (02) ◽  
pp. 193-203 ◽  
Author(s):  
John R Shainoff ◽  
Deborah J Stearns ◽  
Patricia M DiBello ◽  
Youko Hishikawa-Itoh
Keyword(s):  
Peritoneal Macrophages ◽  
Affinity Binding ◽  
Macrophage Cell ◽  
High Affinity Binding ◽  
Amino Terminal ◽  
High Affinity ◽  
Terminal Domain ◽  
Weak Binding ◽  
Amino Terminal Domain

SummaryThe studies reported here probe the existence of a receptor-mediated mode of fibrin-binding by macrophages that is associated with the chemical change underlying the fibrinogen-fibrin conversion (the release of fibrinopeptides from the amino-terminal domain) without depending on fibrin-aggregation. The question is pursued by 1) characterization of binding in relation to fibrinopeptide content of both the intact protein and the CNBr-fragment comprising the amino-terminal domain known as the NDSK of the protein, 2) tests of competition for binding sites, and 3) photo-affinity labeling of macrophage surface proteins. The binding of intact monomers of types lacking either fibrinopeptide A alone (α-fibrin) or both fibrinopeptides A and B (αβ-fibrin) by peritoneal macrophages is characterized as proceeding through both a fibrin-specific low density/high affinity (BMAX ≃ 200–800 molecules/cell, KD ≃ 10−12 M) interaction that is not duplicated with fibrinogen, and a non-specific high density/low affinity (BMAX ≥ 105 molecules/cell, KD ≥ 10−6 M) interaction equivalent to the weak binding of fibrinogen. Similar binding characteristics are displayed by monocyte/macrophage cell lines (J774A.1 and U937) as well as peritoneal macrophages towards the NDSK preparations of these proteins, except for a slightly weaker (KD ≃ 10−10 M) high-affinity binding. The high affinity binding of intact monomer is inhibitable by fibrin-NDSK, but not fibrinogen-NDSK. This binding appears principally dependent on release of fibrinopeptide-A, because a species of fibrin (β-fibrin) lacking fibrinopeptide-B alone undergoes only weak binding similar to that of fibrinogen. Synthetic Gly-Pro-Arg and Gly-His-Arg-Pro corresponding to the N-termini of to the α- and the β-chains of fibrin both inhibit the high affinity binding of the fibrin-NDSKs, and the cell-adhesion peptide Arg-Gly-Asp does not. Photoaffinity-labeling experiments indicate that polypeptides with elec-trophoretically estimated masses of 124 and 187 kDa are the principal membrane components associated with specifically bound fibrin-NDSK. The binding could not be up-regulated with either phorbol myristyl acetate, interferon gamma or ADP, but was abolished by EDTA and by lipopolysaccharide. Because of the low BMAX, it is suggested that the high-affinity mode of binding characterized here would be too limited to function by itself in scavenging much fibrin, but may act cooperatively with other, less limited modes of fibrin binding.

Identification of variable region differences in Neisseria meningitidis class 3 protein sequences among five group B serotypes

1992 ◽  
Vol 6 (23) ◽  
pp. 3493-3499 ◽  
Author(s):  
Gerardo A. Zapata ◽  
Willie F. Vann ◽  
Yaffa Rubinstein ◽  
Carl E. Frasch
Keyword(s):  
Neisseria Meningitidis ◽  
Protein Sequences ◽  
Variable Region ◽  
Group B

scholarly journals Role of Amino-Terminal Domain in the Assembly Mechanism of Kainate-Subtype Glutamate Receptor Ion Channels

2014 ◽  
Vol 106 (2) ◽  
pp. 151a
Author(s):  
Sagar Chittori ◽  
Janesh Kumar ◽  
Suvendu Lomash ◽  
Huaying Zhao ◽  
Peter Schuck ◽  
...  
Keyword(s):  
Ion Channels ◽  
Glutamate Receptor ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Assembly Mechanism ◽  
Amino Terminal Domain

scholarly journals Identification and characterization of a novel cytoskeleton-associated pp60src substrate.

1991 ◽  
Vol 11 (10) ◽  
pp. 5113-5124 ◽  
Author(s):  
H Wu ◽  
A B Reynolds ◽  
S B Kanner ◽  
R R Vines ◽  
J T Parsons
Keyword(s):  
Cell Structure ◽  
Transformed Cells ◽  
Cdna Clones ◽  
Amino Terminal ◽  
Multidomain Structure ◽  
Striking Change ◽  
Carboxyl Terminal ◽  
Amino Terminal Domain ◽  
Related Proteins

Transformation of cells by the src oncogene results in elevated tyrosine phosphorylation of two related proteins, p80 and p85 (p80/85). Immunostaining with specific monoclonal antibodies revealed a striking change of subcellular localization of p80/85 in src-transformed cells. p80/85 colocalizes with F-actin in peripheral extensions of normal cells and rosettes (podosomes) of src-transformed cells. Sequence analysis of cDNA clones encoding p80/85 revealed an amino-terminal domain composed of six copies of a direct tandem repeat, each repeat containing 37 amino acids, a carboxyl-terminal SH3 domain, and an interdomain region composed of a highly charged acidic region and a region rich in proline, serine, and threonine. The multidomain structure of p80/85 and its colocalization with F-actin in normal and src-transformed cells suggest that these proteins may associate with components of the cytoskeleton and contribute to organization of cell structure.

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