scholarly journals The role of negative selection in protein evolution revealed through the energetics of the native state ensemble

2016 ◽  
Vol 84 (4) ◽  
pp. 435-447 ◽  
Author(s):  
Jordan Hoffmann ◽  
James O. Wrabl ◽  
Vincent J. Hilser
Keyword(s):  
Protein Evolution ◽  
Negative Selection ◽  
Native State ◽  
State Ensemble

scholarly journals A Role for Fas in Negative Selection of Thymocytes In Vivo

1998 ◽  
Vol 187 (9) ◽  
pp. 1427-1438 ◽  
Author(s):  
Hidehiro Kishimoto ◽  
Charles D. Surh ◽  
Jonathan Sprent
Keyword(s):  
Negative Selection ◽  
Cell Receptor ◽  
Staphylococcal Enterotoxin B ◽  
Thymic Medulla ◽  
Enterotoxin B ◽  
High Doses ◽  
Specific Peptide ◽  
Selection Of

To seek information on the role of Fas in negative selection, we examined subsets of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice injected with graded doses of antigen. In normal mice, injection of 1–100 μg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vβ8+ cells at the level of the semi-mature population of HSAhi CD4+ 8− cells found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection also caused marked elimination of Vβ8+ HSAhi CD4+ 8− thymocytes in lpr/lpr mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was induced by low-to-moderate doses of SEB (≤1 μg) but not by high doses (100 μg). Similar findings applied when T cell receptor transgenic mice were injected with specific peptide. These findings suggest that clonal elimination of semi-mature medullary T cells is Fas independent at low doses of antigen but Fas dependent at high doses. Previous reports documenting that negative selection is not obviously impaired in lpr/lpr mice could thus reflect that the antigens studied were expressed at only a low level.

scholarly journals Requirement for HLA-DR+ accessory cells in natural killing of cytomegalovirus-infected fibroblasts.

1986 ◽  
Vol 164 (1) ◽  
pp. 180-195 ◽  
Author(s):  
S Bandyopadhyay ◽  
B Perussia ◽  
G Trinchieri ◽  
D S Miller ◽  
S E Starr
Keyword(s):  
Negative Selection ◽  
Target Cells ◽  
Nk Activity ◽  
Ifn Alpha ◽  
Accessory Function ◽  
Hla Dr ◽  
Erythroleukemia Cells ◽  
Accessory Cells ◽  
Selection Experiments

The role of HLA-DR+ cells in NK activity against CMV-infected FS4 foreskin fibroblasts and K562 erythroleukemia cells was examined. When nonadherent PBMC were depleted of either HLA-DR+ or Leu-11b+ cells by treatment with mAbs plus C, NK activity against CMV-FS4 target cells was markedly reduced. In contrast, depletion of HLA-DR+ cells had no effect on NK activity against K562 target cells. When HLA-DR-depleted cells were added to Leu-11b-depleted cells, NK activity against CMV-FS4 was restored. Negative selection experiments indicated that the HLA-DR+ cells contributing to NK activity against CMV-FS4 are not B or T cells, while negative and positive selection experiments excluded a role for monocytes. Experiments in which HLA-DR- and Leu-11b- cells were mixed in varying proportions indicated that NK(CMV-FS4) is mediated by Leu-11b+ cells, while HLA-DR+ cells provide an accessory function. Irradiation (50 GY) abolished the NK effector function of Leu-11b+ cells, but not the accessory function of HLA-DR+ cells. The NK activity against CMV-FS4 of HLA-DR- cells was restored by the addition of rIFN-alpha or of cell-free supernatants generated by coculturing PBMC or Leu-11b- cells with CMV-FS4. The ability of these supernatants to restore NK activity of HLA-DR- cells was completely abrogated by the addition of neutralizing amounts of antibody to IFN-alpha. In related experiments, neutralization of IFN-alpha in NK assays had little or no effect on NK activity against CMV-FS4, suggesting that the accessory function of HLA-DR+ cells might be mediated by alternative mechanisms in addition to the secretion of extracellular IFN-alpha.

Electrophoresis and Electrofocusing of Phytochrome from Etiolated Avena sativa L.

1989 ◽  
Vol 44 (1-2) ◽  
pp. 12-18 ◽  
Author(s):  
Rudolf Schendel ◽  
Wolfhart Rüdiger
Keyword(s):  
Isoelectric Focusing ◽  
Avena Sativa ◽  
Posttranslational Modification ◽  
Negative Charge ◽  
Native State ◽  
Signal Region ◽  
Unfolded State ◽  
Native Gel ◽  
Peptide Region

Abstract Phytochrome from etiolated oat seedlings (Avena sativa L.) was investigated by “native” gel electrophoresis and by isoelectric focusing. At pH 8 . 8 the Pfr form migrated faster than the Pr form in electrophoresis. We assume a difference in the surface charge rather than a difference in shape for the phytochrome forms. This assumption was confirmed by isoelectric focusing which clearly showed relatively more negative charge in the Pfr form than in the Pr form. The role of the peptide region from residue 323 to 360 is discussed in this connection. It carries 9 negatively charged residues, it is exposed only in the Pfr form and it has already been described as a signal region for rapid protein degradation (PEST sequence, see Rogers et al., Science 234, 364-368, 1986). The experiments on electrofocusing revealed a microheterogeneity of phytochrome which was present in the native state as well as in the completely unfolded state. The most probable reason could be either posttranslational modification or genetic polymorphism of phytochrome in oat.

The role of stochasticity on compactness of the native state of protein peptide backbone

2010 ◽  
Vol 133 (8) ◽  
pp. 085102
Author(s):  
P. H. Figueirêdo ◽  
M. A. Moret ◽  
S. Coutinho ◽  
E. Nogueira
Keyword(s):  
Native State ◽  
Peptide Backbone

Structural, energetic, and dynamic responses of the native state ensemble of staphylococcal nuclease to cavity-creating mutations

2013 ◽  
Vol 81 (6) ◽  
pp. 1069-1080 ◽  
Author(s):  
Julien Roche ◽  
Jose A. Caro ◽  
Mariano Dellarole ◽  
Ewelina Guca ◽  
Catherine A. Royer ◽  
...  
Keyword(s):  
Staphylococcal Nuclease ◽  
Dynamic Responses ◽  
Native State ◽  
State Ensemble
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