1,720,979 research outputs found
The possible role of Gly residues in prion octarepeat region in coordination of Cu2+ ions
No full textSpectroscopic and potentiometric data have shown that insertion of tripeptides other than the Gly3 peptide fragment,
Ala3 or Lys3, into the prion octarepeat region destabilizes the biologically relevant Cu2+ complex with the metal ion
bound equatorially through the {Nimid,2N-} donor set. The other likely role of the high glycine content could be
enforcement of the high flexibility of the N-terminal prion region resulting in the unstructured protein organization.
However, the insertion of bulkier amino acid residues does not change the basic coordination mode at physiological
pH which involves imidazole nitrogen and two amide nitrogen donors from the third and fourth residues
Copper-induced structural propensities of the amyloidogenic region of human prion protein
No full textTransmissible spongiform encephalopathies are associated with the misfolding of the cellular Prion Protein (PrPC) to an abnormal protein isoform, called scrapie prion protein (PrPSc). The structural rearrangement of the fragment of N-terminal domain of the protein spanning residues 91-127 is critical for the observed structural transition. The amyloidogenic domain of the protein encloses two copper-binding sites corresponding to His-96 and His-111 residues that act as anchors for metal ion binding. Previous studies have shown that Cu(II) sequestration by both sites may modulate the peptide's tendency to aggregation as it inflicts the hairpin-like structure that stabilizes the transition states leading to beta-sheet formation. On the other hand, since both His sites differ in their ability to Cu(II) sequestration, with His-111 as a preferred binding site, we found it interesting to test the role of Cu(II) coordination to this single site on the structural properties of amyloidogenic domain. The obtained results reveal that copper binding to His-111 site imposes precise backbone bending and weakens the natural tendency of apo peptide to beta-sheet formation
Structural characterization of Cu2+, Ni2+ and Zn2+ binding sites of model peptides associated with neurodegenerative diseases
No full textMetal ions, especially redox active copper, are thought to play critical roles in neurodegenerative disorders. As a matter of fact, metal binding may result into severe conformational changes of proteins involved in neurodegeneration. The present review describes the interactions of metal ions with model peptides mimicking metal binding sites of such proteins, including the prion protein, the β-amyloid and the α-synuclein that have been related to the pathological onset of spongiform encephalopathies, Alzheimer's disease and Parkinson's disease, respectively. Using short protein fragments provides successful tools for characterizing the metal ion interaction with protein domains devoid of any defined secondary structure, and allows one to gain structural information on the metal ion binding properties of the corresponding proteins. Moreover, such an approach based on simplified models yields a multidimensional knowledge that would be never accessible for the natural systems, thus providing a significant and powerful tool for biochemical studies. © 2011 Elsevier B.V
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Copper, zinc and iron in neurodegenerative diseases (Alzheimer's, Parkinson's and prion diseases)
No full textThe basic role of metal ions including copper, zinc and iron in neurological pathologies is generally accepted. The relationship between the development of disease and particular metal ions is very complicated and complex. Thus, comprehension of metal homeostasis, details of transport and interactions with biomolecules is essential for understanding the normal and pathological processes occurring in the living system. Homeostasis of metal ions usually involves a huge set of proteins which regulate the proper metal biology. Disorder in metal homeostasis may result in serious pathologies including neurodegenerative diseases. Metal ions, especially copper, zinc and iron play very important roles in neurodegeneration having impact on both protein structure (misfolding) and oxidative stress. Metal ion binding to proteins involved in neurodegeneration is therefore an important factor for whole brain damage processes. All these aspects are discussed in the review. (C) 2012 Elsevier B.V. All rights reserved
The dimeric and tetrameric octarepeat fragment of prion behaves differently to its monomeric unit
No full textPotentiometric and spectroscopic data have shown that octarepeat dimer and tetramer are much more effective ligands for Cu(II) ions than simple octapeptide. Thus, the whole N-terminal segment of prion protein due to cooperative effects, could be more effective in binding of Cu(II) than simple peptides containing a His residue. The gain of the Cu(II) binding by longer octarepeat peptides derives from the involvement of up to four imidazoles in the coordination of the first Cu(II) ion. This type of binding increases the order of the peptide structure, which allows successive metal ions for easier coordination
Structural analysis of copper(I) interaction with amyloid β peptide
No full textThe N-terminal fragment of Aβ (β = beta) peptide is able to bind essential transition metal ions like, copper, zinc and iron. Metal binding usually occurs via the imidazole nitrogens of the three His residues which play a key role in the coordination chemistry. Among all the investigated systems, the interaction between copper and Amyloid β assume a biological relevance because of the interplay between the two copper oxidation states, Cu(II) and Cu(I), and their involvement in redox reactions. Both copper ions share the ability to bind Amyloid β. A huge number of investigations have demonstrated that Cu(II) anchors to the N-terminal amino and His6, His13/14 imidazole groups, while Cu(I) forms a linear complex by coordinating to the His13 and His14 dyad. In this study we have analyzed Cu(I) interaction with the Amyloid β fragment encompassing the first 16 amino-acids. Our data were obtained by means of NMR spectroscopy which provided relevant structural details of the metal complexes. Our findings are consistent with the involvement of two or three His in the Cu(I) coordination sphere and indicate that His6 effectively participates to the metal binding
Metal binding ability of cysteine-rich peptide domain of ZIP13 Zn 2+ ions transporter
No full textThe coordination modes and thermodynamic stabilities of the complexes of the cysteine-rich N-terminal domain fragment of the ZIP13 zinc transporter (MPGCPCPGCG-NH2) with Zn2+, Cd2+, Bi3+, and Ni2+ have been studied by potentiometric, mass spectrometric, NMR, CD, and UV-vis spectroscopic methods. All of the studied metals had similar binding modes, with the three thiol sulfurs of cysteine residues involved in metal ion coordination. The stability of the complexes formed in solution changes in the series Bi3+ >> Cd2+ > Zn2+ > Ni2+, the strongest being for bismuth and the weakest for nickel. The N-terminal fragment of the human metalothionein-3 (MDPETCPCP-NH2) and unique histidine- and cysteine-rich domain of the C-terminus of Helicobacter pyroli HspA protein (Ac-ACCHDHKKH-NH2) have been chosen for the comparison studies. It confirmed indirectly which groups were the anchoring ones of ZIP 13 domain. Experimental data from all of the used techniques and comparisons allowed us to propose possible coordination modes for all of the studied ZIP13 complexes
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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