The Equilibria of Lipid–K+ Ions in Monolayer at the Air/Water Interface

The effect of K+ ion interaction with monolayers of phosphatidylcholine (lecithin, PC) or cholesterol (Ch) was investigated at the air/water interface. We present surface tension measurements of lipid monolayers obtained using a Langmuir method as a function of K+ ion concentration. Measurements were carried out at 22°C using a Teflon trough and a Nima 9000 tensiometer. Interactions between lecithin and K+ ions or Ch and K+ ions result in significant deviations from the additivity rule. An equilibrium theory to describe the behavior of monolayer components at the air/water interface was developed in order to obtain the stability constants and area occupied by one molecule of lipid–K+ ion complex (LK+). The stability constants for lecithin–K+ ion (PCK+) complex, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$K_{{{\text{PCK}}^{ + } }} = { 3}. 2 6\times 10^{ 2} {\text{dm}}^{ 3} \,{\text{mol}}^{ - 1}$$\end{document}, and for cholesterol–K+ ion (ChK+) complex, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$K_{{{\text{ChK}}^{ + } }} = { 1}.00 \times 10^{ 3} {\text{dm}}^{ 3} \,{\text{mol}}^{ - 1}$$\end{document}, were calculated by inserting the experimental data. The value of area occupied by one PCK+ complex is 60 Å2 molecule−1, while the area occupied by one ChK+ complex is 40.9 Å2 molecule−1. The complex formation energy (Gibbs free energy) values for the PCK+ and ChK+ complexes are −14.18 ± 0.71 and −16.92 ± 0.85 kJ mol−1, respectively

Interactions of Cu(2+) with prion family peptide fragments: Considerations on affinity, speciation and coordination

The review describes the stability and the coordination modes of Cu(2+) complexes with different regions of N-terminus prion proteins. The structural features of the different metal species are correlated both with the Cu(2+)-driven redox properties and with the conformational changes induced by the Cu(2+) in the different metal binding regions of the protein. The formation of mixed metal complexes is also discussed. We emphasize that binding features should be discussed by referring to the species that actually forms under specific conditions (pH, buffer, etc.) rather than to the "binding site"; correlating properties with the structures of the so called 'binding sites' may lead to misinterpretation of the experimental results, since a 'binding site' often corresponds to a mixture of species. We also highlight that ignoring species that form with ligands other than the prion peptide (e.g. the buffer) may lead to underestimating their role in crucial processes (e.g. redox activity)

Coordination features of prion protein domains

Many systemic and neurodegenerative disorders, collectively termed as “protein conformational diseases” are characterized by the accumulation of intracellular or extracellular protein aggregates. Abnormal metal-protein interactions have now been implicated in some of these degenerative disorders including Alzheimer’s disease, cataracts, Parkinson’s, Creutzfeldt-Jakob disease, etc.). Prion diseases provide a typical example in which the conversion of the normal folded α-helical PrPC isoform into a β-sheet rich conformation PrPSc, results in neurodegeneration. The physiological function of PrPC has not yet been identified, even though it is emerging that this highly conserved protein is important for a healthy brain. Increasing evidence indicates that PrPc is a copper-binding protein, and its localisation at pre and postsynaptic levels suggests an involvement in copper uptake and transmembrane signalling. Copper(II)-PrPC studies can be problematic due to the formation of PrPc insoluble species, therefore different protein fragments have been used to determine the metalprotein stoichiometry, the copper(II) affinity of different regions, the binding sites and the coordination features of the resulting metal complexes. Conflicting results have been reported, probably due to an oversimplification of metal complex speciation. A combined thermodynamic and spectroscopic approach has been recently used to characterize the coordination features of different prion domains. The results questioned the role of octarepeats present in the unstructured N-terminus region as the main binding site for copper(II), rather suggesting preferential metal coordination outside of the octarepeat region. Furthermore, comparative analysis of the human and chicken PrP copper(II) binding sites may provide new insights into the prion protein structure-function relationship and the conversion process of PrP