Role of the N-Terminal Helix in the Metal Ion-Induced Activation of the Diphtheria Toxin Repressor DtxR

Biochemistry ◽  
2007 ◽  
Vol 46 (42) ◽  
pp. 11761-11770 ◽  
Author(s):  
J. Alejandro D'Aquino ◽  
Judith R. Lattimer ◽  
Andrew Denninger ◽  
Katharine E. D'Aquino ◽  
Dagmar Ringe
Keyword(s):  
Diphtheria Toxin ◽  
Metal Ion ◽  
Diphtheria Toxin Repressor

Structure of the metal-ion-activated diphtheria toxin repressor/ tox operator complex

Nature ◽  
10.1038/28893 ◽  
1998 ◽  
Vol 394 (6692) ◽  
pp. 502-506 ◽  
Author(s):  
André White ◽  
Xiaochun Ding ◽  
Johanna C. vanderSpek ◽  
John R. Murphy ◽  
Dagmar Ringe
Keyword(s):  
Diphtheria Toxin ◽  
Metal Ion ◽  
Diphtheria Toxin Repressor

Diphtheria Toxin Repressor: Metal Ion Mediated Control of Transcription

2006 ◽  
Author(s):  
Dagmar Ringe ◽  
Andre White ◽  
Shuyan Chen ◽  
John R Murphy
Keyword(s):  
Diphtheria Toxin ◽  
Metal Ion ◽  
Diphtheria Toxin Repressor

scholarly journals Mechanism of metal ion activation of the diphtheria toxin repressor DtxR

2005 ◽  
Vol 102 (51) ◽  
pp. 18408-18413 ◽  
Author(s):  
J. A. D'Aquino ◽  
J. Tetenbaum-Novatt ◽  
A. White ◽  
F. Berkovitch ◽  
D. Ringe
Keyword(s):  
Diphtheria Toxin ◽  
Metal Ion ◽  
Ion Activation ◽  
Diphtheria Toxin Repressor ◽  
Metal Ion Activation

scholarly journals The src Homology 3-Like Domain of the Diphtheria Toxin Repressor (DtxR) Modulates Repressor Activation through Interaction with the Ancillary Metal Ion-Binding Site

2003 ◽  
Vol 185 (7) ◽  
pp. 2251-2258 ◽  
Author(s):  
John F. Love ◽  
Johanna C. vanderSpek ◽  
John R. Murphy
Keyword(s):  
Transition Metal ◽  
Binding Site ◽  
Diphtheria Toxin ◽  
Metal Ion ◽  
Ion Binding ◽  
Metal Ion Binding ◽  
Binding Studies ◽  
Transition Metal Ion ◽  
Diphtheria Toxin Repressor

ABSTRACT The diphtheria toxin repressor (DtxR) is a transition metal ion-activated repressor that acts as a global regulatory element in the control of iron-sensitive genes in Corynebacterium diphtheriae. We recently described (L. Sun, J. C. vanderSpek, and J. R. Murphy, Proc. Natl. Acad. Sci. USA 95:14985-14990, 1998) the isolation and in vivo characterization of a hyperactive mutant of DtxR, DtxR(E175K), that appeared to be constitutively active. We demonstrate here that while DtxR(E175K) remains active in vivo in the presence of 300 μM 2,2′dipyridyl, the purified repressor is, in fact, dependent upon low levels of transition metal ion to transit from the inactive apo form to the active metal ion-bound form of the repressor. Binding studies using 8-anilino-1-naphthalenesulfonic acid suggest that the E175K mutation stabilizes an intermediate of the molten-globule form of the repressor, increasing exposure of hydrophobic residues to solvent. We demonstrate that the hyperactive DtxR(E175K) phenotype is dependent upon an intact ancillary metal ion-binding site (site 1) of the repressor. These observations support the hypothesis that metal ion binding in the ancillary site facilitates the conversion of the inactive apo-repressor to its active, operator-binding conformation. Furthermore, these results support the hypothesis that the C-terminal src homology 3-like domain of DtxR plays an active role in the modulation of repressor activity.

scholarly journals CD206+ macrophage is an accelerator of endometriotic-like lesion via promoting angiogenesis in the endometriosis mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yosuke Ono ◽  
Osamu Yoshino ◽  
Takehiro Hiraoka ◽  
Erina Sato ◽  
Akiko Furue ◽  
...  
Keyword(s):  
Mouse Model ◽  
Diphtheria Toxin ◽  
Immunohistochemical Study ◽  
Mrna Levels ◽  
Cytokines And Chemokines ◽  
Diphtheria Toxin Receptor ◽  
Endothelial Cell Marker ◽  
Toxin Receptor ◽  
Group A

AbstractIn endometriosis, M2 MΦs are dominant in endometriotic lesions, but the actual role of M2 MΦ is unclear. CD206 positive (+) MΦ is classified in one of M2 type MΦs and are known to produce cytokines and chemokines. In the present study, we used CD206 diphtheria toxin receptor mice, which enable to deplete CD206+ cells with diphtheria toxin (DT) in an endometriosis mouse model. The depletion of CD206+ MΦ decreased the total weight of endometriotic-like lesions significantly (p < 0.05). In the endometriotic-like lesions in the DT group, a lower proliferation of endometriotic cells and the decrease of angiogenesis were observed. In the lesions, the mRNA levels of VEGFA and TGFβ1, angiogenic factors, in the DT group significantly decreased to approximately 50% and 30% of control, respectively. Immunohistochemical study revealed the expressions of VEGFA and an endothelial cell marker CD31 in lesions of the DT group, were dim compared to those in control. Also, the number of TGFβ1 expressing MΦ was significantly reduced compared to control. These data suggest that CD206+ MΦ promotes the formation of endometriotic-like lesions by inducing angiogenesis around the lesions.

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