Desmin mutations in the terminal consensus motif prevent synemin-desmin heteropolymer filament assembly.

Disorganization of the desmin network is associated with cardiac and skeletal myopathies characterized by accumulation of desmin-containing aggregates in the cells. Multiple associations of intermediate filament proteins form a network to increase mechanical and functional stability. Synemin is a desmin-associated type VI intermediate filament protein.

Loss of a DNA binding site within the tail of prelamin A contributes to altered heterochromatin anchorage by progerin.

Mutations in the lamin A/C (LMNA) gene that cause Hutchinson-Gilford progeria syndrome (HGPS) lead to expression of a protein called progerin with 50 amino acids deleted from the tail of prelamin A. In cells from patients with HGPS, both the amount and distribution of heterochromatin are altered. We designed in vitro assays to ask whether such alterations might reflect changes in chromatin, DNA and/or histone binding properties of progerin compared to wild-type lamin C-terminal tails.

Desmin myopathy with severe cardiomyopathy in a Uruguayan family due to a codon deletion in a new location within the desmin 1A rod domain.

Desmin myopathy is a heterogeneous neuromuscular disorder characterized by skeletal myopathy and cardiomyopathy, inherited mostly in an autosomal dominant pattern. We report a five generation Uruguayan family with severe cardiomyopathy and skeletal myopathy. Its most striking features are: atrial dilation, arrhythmia, conduction block and sudden death due to conduction impairment.

Structural requirements for antimicrobial versus chemoattractant activities for dermaseptin S9.

Dermaseptin S9 (Drs S9), GLRSKIWLWVLLMIWQESNKFKKM, isolated from frog skin, does not resemble any of the cationic and amphipathic antimicrobial peptides identified to date, having a highly hydrophobic core sequence flanked at either side by cationic termini. Previous studies [Lequin O, Ladram A, Chabbert A, Bruston F, Convert O, Vanhoye D, Chassaing G, Nicolas P & Amiche M (2006) Biochemistry45, 468-480] demonstrated that this peptide adopted a non-amphipathic alpha-helical conformation in trifluoroethanol/water mixtures, but was highly aggregated in aqueous solutions and in the presence of sodium dodecyl sulfate micelles. Circular dichroism, FTIR and attenuated total reflectance FTIR spectroscopies, combined with a surface plasmon resonance study, show that Drs S9 forms stable and ordered beta-sheet aggregates in aqueous buffers or when bound to anionic or zwitterionic phospholipid vesicles.

Intrinsic flexibility and structural adaptability of Plasticins membrane-damaging peptides as a strategy for functional versatility.

The Plasticins are a family of antimicrobial, 23-29-residue Gly-Leu-rich ortholog peptides from the frog skin that have very similar amino acid sequences, hydrophobicities, and amphipathicities but differ markedly in their conformational plasticity and spectrum of activity. The intrinsic flexibility and structural malleability of Plasticins modulate their ability to bind to and disrupt the bilayer membranes of prokaryotic and eukaryotic cells, and/or to reach intracellular targets, therefore, triggering functional versatility. The discussion is opened herein on several examples of other membrane-active peptides, like viral fusion peptides, cell-penetrating peptides, that are able to display antimicrobial activity.

Structural malleability of plasticins: preorganized conformations in solution and relevance for antimicrobial activity.

Plasticins (23 long-residue glycine-leucine-rich dermaseptin-related peptides produced by the skin of South American hylids) have very similar amino acid sequences, hydrophobicities, and amphipathicities, but differ in their membrane-damaging properties and structurations (i.e. destabilized helix states, beta-hairpin, beta-sheet, and disordered states) at anionic and zwitterionic membrane interfaces.

The plasticins: membrane adsorption, lipid disorders, and biological activity.

The present study investigates the relationships between structural polymorphism, adsorption onto membrane mimetic support, lipid disturbance, and biological activity of bactericidal 23-residue, glycine-leucine-rich dermaseptin orthologues from the Phyllomedusinae frog skin, the "plasticins". Biological activities were evaluated using the membrane models DMPG (1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol) for prokaryotic membranes and DMPC (1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine) for eukaryotic membranes. We performed a conformational analysis of plasticins by molecular simulations and spectroscopic methods and analyzed phospholipid perturbations by infrared spectroscopy.

Dermaseptin S9, an alpha-helical antimicrobial peptide with a hydrophobic core and cationic termini.

The dermaseptins S are closely related peptides with broad-spectrum antibacterial activity that are produced by the skin of the South American hylid frog, Phyllomedusa sauvagei. These peptides are polycationic (Lys-rich), alpha-helical, and amphipathic, with their polar/charged and apolar amino acids on opposing faces along the long axis of the helix cylinder. The amphipathic alpha-helical structure is believed to enable the peptides to interact with membrane bilayers, leading to permeation and disruption of the target cell.

Membrane association, electrostatic sequestration, and cytotoxicity of Gly-Leu-rich peptide orthologs with differing functions.

The skins of closely related frog species produce Gly-Leu-rich peptide orthologs that have very similar sequences, hydrophobicities, and amphipathicities but differ markedly in their net charge and membrane-damaging properties. Cationic Gly-Leu-rich peptides are hemolytic and very potent against microorganisms. Peptides with no net charge have only hemolytic activity.

Helical structure of dermaseptin B2 in a membrane-mimetic environment.

Dermaseptins are antimicrobial peptides from frog skin that have high membrane-lytic activity against a broad spectrum of microorganisms. The structure of dermaseptin B2 in aqueous solution, in TFE/water mixtures, and in micellar and nonmicellar SDS was analyzed by CD, FTIR, fluorescence, and NMR spectroscopy combined with molecular dynamics calculations. Dermaseptin B2 is unstructured in water, but helical conformations, mostly in segment 3-18, are stabilized by addition of TFE.

Conformation, orientation, and adsorption kinetics of dermaseptin B2 onto synthetic supports at aqueous/solid interface.

The antimicrobial activity of cationic amphipathic peptides is due mainly to the adsorption of peptides onto target membranes, which can be modulated by such physicochemical parameters as charge and hydrophobicity. We investigated the structure of dermaseptin B2 (Drs B2) at the aqueous/synthetic solid support interface and its adsorption kinetics using attenuated total reflection Fourier transform infrared spectroscopy and surface plasmon resonance. We determined the conformation and affinity of Drs B2 adsorbed onto negatively charged (silica or dextran) and hydrophobic supports.

Antimicrobial peptides from hylid and ranin frogs originated from a 150-million-year-old ancestral precursor with a conserved signal peptide but a hypermutable antimicrobial domain.

The dermal glands of frogs produce antimicrobial peptides that protect the skin against noxious microorganisms and assist in wound repair. The sequences of these peptides are very dissimilar, both within and between species, so that the 5000 living anuran frogs may produce approximately 100 000 different antimicrobial peptides. The antimicrobial peptides of South American hylid frogs are derived from precursors, the preprodermaseptins, whose signal peptides and intervening sequences are remarkably conserved, but their C-terminal domains are markedly diverse, resulting in mature peptides with different lengths, sequences and antimicrobial spectra.

A possible role of the Na(+)/K(+)-ATPase for O(2) production from H(2)O(2).

We are attempting to supply a new insight on interaction between Na(+)/K(+)-ATPase and H(2)O(2). We demonstrate that in vitro the Na(+)/K(+)-ATPase, a non heme-protein, is able to disproportionate H(2)O(2) catalatically into dioxygen and water, as well as C(40) catalase. By polarography, we quantify O(2) production and by Raman spectroscopy H(2)O(2) consumption.

Copper-adenine catalyst for O(2) production from H(2)O(2).

In solutions of CuCl2 and adenine copper can be bound to adenine. Two Cu(adenine)(2) complexes [Cu(C(5)H(5)N(5))(2)]2+/Cu(C(5)H(4)N(5))(2)] are in equilibrium with free adenine. Copper-adenine complexes present a catalytic activity (e.