Energetics of gating MscS by membrane tension in azolectin liposomes and giant spheroplasts

<div><p>Mechanosensitive (MS) ion channels are molecular sensors that detect and transduce signals across prokaryotic and eukaryotic cell membranes arising from external mechanical stimuli or osmotic gradients. They play an integral role in mechanosensory responses including touch, hearing, and proprioception by opening or closing in order to facilitate or prevent the flow of ions and organic osmolytes. In this study we use a linear force model of MS channel gating to determine the gating membrane tension (γ) and the gating area change (ΔA) associated with the energetics of MscS channel gating in giant spheroplasts and azolectin liposomes. Analysis of Boltzmann distribution functions describing the dependence of MscS channel gating on membrane tension indicated that the gating area change (ΔA) was the same for MscS channels recorded in both preparations. The comparison of the membrane tension (γ) gating the channel, however, showed a significant difference between the MscS channel activities in these two preparations.</p></div

Model Study Using Designed Selenopeptides on the Importance of the Catalytic Triad for the Antioxidative Functions of Glutathione Peroxidase

Although the catalytic triad of glutathione peroxidase (GPx) has been well recognized, there was little evidence for the relevance of the interactions among the triad amino acid residues, i.e., selenocysteine (U), glutamine (Q), and tryptophan (W), to the GPx antioxidative functions. Using a designed selenopeptide having an amino acid sequence of GQAUAWG, we demonstrate here that U, Q, and W present at the active site can interact with each other to exert the enzymatic activity. The amino acid sequence was chosen on the basis of the Monte Carlo molecular simulation for various selenopeptides in polarizable continuous water using the SAAP force field (SAAP-MC). Measurement of the GPx-like activity for the selenopeptide obtained by solid-phase peptide synthesis revealed that the antioxidant activity is cooperatively enhanced by the presence of Q and W proximate to U, although the activity was low compared to selenocystine (U₂). The effect of Q on the activity was more important than that of W. In addition, the fluorescence spectrometry suggested a close contact between U and W. These experimental observations were supported by SAAP-MC simulation as well as by ab initio calculation. The latter further suggested that the interaction mode among the triad changes depending on the intermediate states

Multi-layered mutations were observed in the four study subjects with Gorlin syndrome.

<p>Multi-layered mutations were observed in the four study subjects with Gorlin syndrome.</p

Disease-causing mutated gene.

<p>Disease-causing mutated gene.</p

Flow chart indicating the validation process for variants.

<p>After the validation steps, 61 variations were selected.</p

Gene list for 84 genes.

<p>Gene list for 84 genes.</p

Six major criteria by Kimonis and the PTCH1 mutation in the four study subjects with Gorlin syndrome.

<p>Six major criteria by Kimonis and the PTCH1 mutation in the four study subjects with Gorlin syndrome.</p

Panoramic radiograph demonstrates the presence of odontgenic keratocysts.

<p>Radiologic images showed odontogenic keratocystes in each individual. Yellow arrows showed radiolucent lesions.</p