A Functional Role for Aβ in Metal Homeostasis? N-Truncation and High-Affinity Copper Binding

2015 ◽  
Vol 127 (36) ◽  
pp. 10606-10610 ◽  
Author(s):  
Mariusz Mital ◽  
Nina E. Wezynfeld ◽  
Tomasz Frączyk ◽  
Magdalena Z. Wiloch ◽  
Urszula E. Wawrzyniak ◽  
...  
Keyword(s):  
Functional Role ◽  
Metal Homeostasis ◽  
Copper Binding ◽  
High Affinity

A Functional Role for Aβ in Metal Homeostasis? N-Truncation and High-Affinity Copper Binding

2015 ◽  
Vol 54 (36) ◽  
pp. 10460-10464 ◽  
Author(s):  
Mariusz Mital ◽  
Nina E. Wezynfeld ◽  
Tomasz Frączyk ◽  
Magdalena Z. Wiloch ◽  
Urszula E. Wawrzyniak ◽  
...  
Keyword(s):  
Functional Role ◽  
Metal Homeostasis ◽  
Copper Binding ◽  
High Affinity

XAFS study of the high-affinity copper-binding site of human PrP 91–231 and its low-resolution structure in solution 1 1Edited by I. A. Wilson

2001 ◽  
Vol 311 (3) ◽  
pp. 467-473 ◽  
Author(s):  
S.Samar Hasnain ◽  
Loretta M. Murphy ◽  
Richard W. Strange ◽  
J.Günter Grossmann ◽  
Anthony R. Clarke ◽  
...  
Keyword(s):  
Binding Site ◽  
Copper Binding ◽  
Low Resolution ◽  
High Affinity ◽  
Structure In Solution ◽  
Resolution Structure

scholarly journals High affinity copper binding by stefin B (cystatin B) and its role in the inhibition of amyloid fibrillation

FEBS Journal ◽  
2006 ◽  
Vol 273 (18) ◽  
pp. 4250-4263 ◽  
Author(s):  
Eva Žerovnik ◽  
Katja Škerget ◽  
Magda Tušek-Žnidarič ◽  
Corina Loeschner ◽  
Marcus W. Brazier ◽  
...  
Keyword(s):  
Copper Binding ◽  
Cystatin B ◽  
High Affinity ◽  
Amyloid Fibrillation

Role of the α-subunit326GRV sequence in the surface expression of fibrinogen and vitronectin receptors

1998 ◽  
Vol 275 (5) ◽  
pp. C1239-C1246 ◽  
Author(s):  
Milagros Ferrer ◽  
Matilde S. Ayuso ◽  
Nora Butta ◽  
Roberto Parrilla ◽  
Consuelo González-Manchón
Keyword(s):  
Functional Role ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Surface Expression ◽  
Platelet Surface ◽  
Α Subunit ◽  
Vitronectin Receptor ◽  
Ovary Cells ◽  
High Affinity

The platelet GPIIb-GPIIIa heterodimer (integrin αIIbβ3) binds fibrinogen with high affinity in response to activation by agonists, leading to platelet aggregation and formation of a hemostatic plug. The326GRV motif in GPIIb is highly conserved in the α-subunit of other integrins, suggesting that it might play an important functional role. Moreover, Arg327→His substitution in GPIIb has been associated with defective platelet surface expression of GPIIb-IIIa and thrombasthenic phenotype. This work aimed at elucidating whether the absence of Arg327or its substitution by His was responsible for the impaired surface expression of GPIIb-IIIa complexes. Transfection of cDNA encoding [Ala327]GPIIb, [Gln327]GPIIb, or [Phe327]GPIIb into Chinese hamster ovary cells inherently expressing GPIIIa permitted surface exposure of GPIIb-IIIa complexes, whereas [Glu327]GPIIb did not. These observations indicate that it is not the loss of [Arg327]GPIIb but the presence of His327or a negatively charged residue like Glu at position 327 of GPIIb that prevents the surface exposure of GPIIb-IIIa heterodimers. In contrast, changing Gln344, the homologue to Arg327in the α-subunit of the vitronectin receptor, to His did not prevent the surface expression of αv-GPIIIa complexes. Thus the conformational constraint imposed by His327seems to be rather specific for the heterodimerization and/or processing of GPIIb-IIIa complexes.

Identification of a novel high affinity copper binding site in the APP(145–155) fragment of amyloid precursor protein

2004 ◽  
pp. 16-22 ◽  
Author(s):  
Daniela Valensin ◽  
Francesca Maria Mancini ◽  
Marek Łuczkowski ◽  
Anna Janicka ◽  
Kornelia Wiśniewska ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Binding Site ◽  
Precursor Protein ◽  
Copper Binding ◽  
High Affinity

Involvement of nitrogen functional groups in high-affinity copper binding in tomato and wheat root apoplasts: spectroscopic and thermodynamic evidence

Metallomics ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 366-376 ◽  
Author(s):  
Stéphanie Guigues ◽  
Matthieu N. Bravin ◽  
Cédric Garnier ◽  
Armand Masion ◽  
Claire Chevassus-Rosset ◽  
...  
Keyword(s):  
Functional Groups ◽  
Local Environment ◽  
Wheat Root ◽  
Copper Binding ◽  
High Affinity

A dual local environment of Cu in root apoplasts was identified.

scholarly journals Role for dithiolopyrrolones in disrupting bacterial metal homeostasis

2017 ◽  
Vol 114 (10) ◽  
pp. 2717-2722 ◽  
Author(s):  
Andrew N. Chan ◽  
Anthony L. Shiver ◽  
Walter J. Wever ◽  
Sayyeda Zeenat A. Razvi ◽  
Matthew F. Traxler ◽  
...  
Keyword(s):  
Natural Products ◽  
Rna Polymerase ◽  
Metal Binding ◽  
Antimicrobial Activities ◽  
Metal Homeostasis ◽  
Chemical Genomics ◽  
Chemical Structures ◽  
High Affinity ◽  
Metal Chelating

Natural products harbor unique and complex structures that provide valuable antibiotic scaffolds. With an increase in antibiotic resistance, natural products once again hold promise for new antimicrobial therapies, especially those with unique scaffolds that have been overlooked due to a lack of understanding of how they function. Dithiolopyrrolones (DTPs) are an underexplored class of disulfide-containing natural products, which exhibit potent antimicrobial activities against multidrug-resistant pathogens. DTPs were thought to target RNA polymerase, but conflicting observations leave the mechanisms elusive. Using a chemical genomics screen inEscherichia coli, we uncover a mode of action for DTPs—the disruption of metal homeostasis. We show that holomycin, a prototypical DTP, is reductively activated, and reduced holomycin chelates zinc with high affinity. Examination of reduced holomycin against zinc-dependent metalloenzymes revealed that it inhibitsE. coliclass II fructose bisphosphate aldolase, but not RNA polymerase. Reduced holomycin also strongly inhibits metallo–β-lactamases in vitro, major contributors to clinical carbapenem resistance, by removing active site zinc. These results indicate that holomycin is an intracellular metal-chelating antibiotic that inhibits a subset of metalloenzymes and that RNA polymerase is unlikely to be the primary target. Our work establishes a link between the chemical structures of DTPs and their antimicrobial action; the ene-dithiol group of DTPs enables high-affinity metal binding as a central mechanism to inhibit metabolic processes. Our study also validates the use of chemical genomics in characterizing modes of actions of antibiotics and emphasizes the potential of metal-chelating natural products in antimicrobial therapy.

scholarly journals Expression and functional role of tumor necrosis factor receptors on leukemic cells from patients with type B chronic lymphoproliferative disorders

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 752-758 ◽  
Author(s):  
L Trentin ◽  
R Zambello ◽  
C Agostini ◽  
F Siviero ◽  
F Adami ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Functional Role ◽  
Tumor Necrosis ◽  
Leukemic Cells ◽  
Tnf Alpha ◽  
High Affinity ◽  
Necrosis Factor

Abstract Two receptors for tumor necrosis factor (TNF) with different molecular weight (75-Kd and 55-Kd) and binding affinity have been recently discovered. To investigate the distribution and the functional role of these receptors on leukemic B cells from hairy cell leukemia (HCL) and B-cell chronic lymphocytic leukemia (B-CLL) patients, we evaluated: (1) the cytofluorimetric pattern of uncultured and cultured leukemic B cells incubated with utr-1 and htr-9 monoclonal antibodies (MoAbs), which specifically recognize the 75-Kd and 55-Kd TNF receptors (TNFR), respectively; (2) the effect of TNF-alpha and TNF-beta on leukemic B cells in an in vitro proliferation assay; (3) the role of anti-TNFR MoAbs on TNF-alpha and TNF-beta-driven B-cell growth; and (4) the proliferative effect of utr-1 and htr-9 MoAbs on in vitro cultured leukemic cells. Our study shows that the high affinity (75-Kd) but not the low affinity (55-Kd) TNFR molecules are expressed on freshly isolated leukemic B cells recovered from HCL and B-CLL patients. The expression of these receptors was neither upregulated nor downregulated by different stimuli, including TNF-alpha, TNF-beta, B-cell growth factor, and interleukin-2. TNF-alpha efficiently triggers the proliferation of HC and, to a lesser extent, the growth of B-CLL cells. TNF-beta was also able to transduce the proliferative signal in HCL, but not in B-CLL patients. TNF-alpha- and TNF-beta-driven B-cell proliferation was inhibited by the preincubation of leukemic B cells with utr-1 but not htr-9 MoAb. Moreover, anti-75-Kd, but not anti-55-Kd TNFR MoAb, was able to trigger the proliferation of leukemic B cells, and in particular of HC. These results show that leukemic B cells from patients with HCL and B-CLL are equipped with a fully functional high affinity TNFR.

scholarly journals Glycosaminoglycans can modulate extracellular localization of the wingless protein and promote signal transduction.

1996 ◽  
Vol 135 (3) ◽  
pp. 819-827 ◽  
Author(s):  
F Reichsman ◽  
L Smith ◽  
S Cumberledge
Keyword(s):  
Cell Surface ◽  
Functional Role ◽  
Noncovalent Interactions ◽  
S2 Cells ◽  
Biochemical Mechanism ◽  
High Affinity ◽  
Agarose Beads ◽  
Naturally Occurring ◽  
Differentiation And Proliferation ◽  
Lines Of Evidence

Wingless, the Drosophila homologue of the proto-oncogene Wnt-1, encodes a secreted glycoprotein that regulates differentiation and proliferation of nearby cells. Here we report on the biochemical mechanism(s) by which the wingless signal is transmitted from cell to cell. When expressed in S2 cells, the majority (approximately 83%) of secreted wingless protein (WG) is bound to the cell surface and extracellular matrix through specific, noncovalent interactions. The tethered WG can be released by addition of exogenous heparan sulfate and chondroitin sulfate glycosaminoglycans. WG also binds directly to heparin agarose beads with high affinity. These data suggest that WG can bind to the cell surface via naturally occurring sulfated proteoglycans. Two lines of evidence indicate that extracellular glycosaminoglycans on the receiving cells also play a functional role in WG signaling. First, treatment of WG-responsive cells with glycosaminoglycan lyases reduced WG activity by 50%. Second, when WG-responsive cells were preincubated with 1 mM chlorate, which blocks sulfation, WG activity was inhibited to near-basal levels. Addition of exogenous heparin to the chlorate-treated cells was able to restore WG activity. Based on these results, we propose that WG belongs to the group of growth factor ligands whose actions are mediated by extracellular proteoglycan molecules.

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