Folding of VemP into translation-arresting secondary structure is driven by the ribosome exit tunnel

The ribosome is a fundamental biomolecular complex that synthesizes proteins in cells. Nascent proteins emerge from the ribosome through a tunnel, where they may interact with the tunnel walls or small molecules such as antibiotics. These interactions can cause translational arrest with notable physiological consequences. Here, we studied the arrest caused by the regulatory peptide VemP, which is known to form α-helices inside the ribosome tunnel near the peptidyl transferase center under specific conditions. We used all-atom molecular dynamics simulations of the entire ribosome and circular dichroism spectroscopy to study the driving forces of helix formation and how VemP causes the translational arrest. To that aim, we compared VemP dynamics in the ribosome tunnel with its dynamics in solution. We show that the VemP peptide has a low helical propensity in water and that the propensity is higher in mixtures of water and trifluorethanol. We propose that helix formation within the ribosome is driven by the interactions of VemP with the tunnel and that a part of VemP acts as an anchor. This anchor might slow down VemP progression through the tunnel enabling α-helix formation, which causes the elongation arrest.     

Experimentelle Untersuchungen zur Anpassung von Fungiiden (Scleractinia,Fungiidae). an unterschiedliche Sedimentations-und Bodenverhältnisse.

Experiments on Adaptations to Sedimentation and Substrate in Fungiid Corals (Scleractinia, Fungiidae) Experimental evaluation of the sediment rejecting behaviour in fungiid corals shows: a). sediments easily slide off from cupolate coralla; b). some flat corals inflate the polyp to get rid off sediments; c). in most species sediments are entangled in mucus and removed by ciliary action. However mucus production is limited by the number of functioning mucous cells. During continuous stress by weighting sediments the tissue overlying the septal ridges gets cut and worn off. Damage instantly occurs in species with sharp septa, but relatively late in those with broad septa. Even minute tissue remains are capable of regenerating trophozoids attached to the old skeleton. Species which endure only low sedimentation rates, are mainly confined to hard bottoms (e.g. reef slope).     

Die Cuticula der Epidermis des Regenwurms (Lumbricus terrestris L.)

Zusammenfassung Die um 3–4 dicke Cuticula des Regenwurms (Lumbricus terrestris L.) besteht aus 20–30 sich annähernd rechtwinklig kreuzenden Lagen von Cuticulafibrillen. Senkrecht zu und zwischen den sich kreuzenden Fibrillen verlaufen röhrenförmige Zellfortsätze, Cuticulakanälchen von der Oberfläche der Epithelzelle zur Epicuticula. Die Epicuticula bildet eine kontinuierliche, mit feinen, dicht stehenden Exkreszenzen besetzte Schicht. Die zelluläre, respektive extrazelluläre Natur der Cuticulastrukturen und ihr funktionelles Verhalten werden besprochen. Anmerkung bei der Korrektur. Die Herren D. Peters (Hamburg) und W. J. Schmidt (Gießen) machten uns auf die Untersuchung der Cuticulastruktur des Regenwurms durch Reed und Rudall (1948) aufmerksam.Die von den englischen Autoren gewonnenen Abdruckpräparate aus verschieden tiefen Schichten der Cuticula stimmen mit den hier gezeigten Schnittpräparaten vorzüglich überein und ergänzen sie durch die Aufsicht auf die freie Oberfläche. Mit der Abdrucktechnik sind jedoch die Cuticula-Kanälchen zwischen den Fibrillen nicht erkannt worden. Einige der Vermutungen über die Bildung der Cuticulafibrulen (s. auch Rudall 1950) dürften deshalb hinfällig geworden sein. Über die chemische Zusammensetzung der Cuticula und ihre chemischen Unterschiede gegenüber Kollagen s. Watson und Smith (1956).Mit dankenswerter Unterstützung durch das Kultusministerium des Landes Nordrhein-Westfalen durchgeführte Untersuchung.     

Diazaborine treatment of yeast cells inhibits maturation of the 60S ribosomal subunit

Diazaborine treatment of yeast cells was shown previously to cause accumulation of aberrant, 3'-elongated mRNAs. Here we demonstrate that the drug inhibits maturation of rRNAs for the large ribosomal subunit. Pulse-chase analyses showed that the processing of the 27S pre-rRNA to consecutive species was blocked in the drug-treated wild-type strain. The steady-state level of the 7S pre-rRNA was clearly reduced after short-term treatment with the inhibitor. At the same time an increase of the 35S pre-rRNA was observed. Longer incubation with the inhibitor resulted in a decrease of the 27S precursor. Primer extension assays showed that an early step in 27S pre-rRNA processing is inhibited, which results in an accumulation of the 27SA2 pre-rRNA and a strong decrease of the 27SA3, 27SB1L, and 27SB1S precursors. The rRNA processing pattern observed after diazaborine treatment resembles that reported after depletion of the RNA binding protein Nop4p/Nop77p. This protein is essential for correct pre-27S rRNA processing. Using a green fluorescent protein-Nop4 fusion, we found that diazaborine treatment causes, within minutes, a rapid redistribution of the protein from the nucleolus to the periphery of the nucleus, which provides a possible explanation for the effect of diazaborine on rRNA processing.     

The velocity of calcium waves is expected to depend non-monotonously on the density of the calcium release units

In this paper we develop a reaction-diffusion system describing the calcium dynamics in an agarose gel system with resuspended vesicles from the sarcoplasmic reticulum (SR vesicles). We focus on a simple model: compared with living cells (e.g. cardiac myocytes) an important property of the agarose gel system is the absence of the sarcolemma and the spatial separation of the calcium release units (CRUs). Our model includes the kinetics of ryanodine sensitive receptors (RyRs), the activity of the SERCA pumps and the diffusion of free calcium. We describe numerical simulations which show a biphasic relationship between the density of the CRUs and the propagation velocity of spreading waves. The non-monotony can be explained by changes in the amplitude of the local calcium concentration. We formulate implications for the in vitro system which could be verified in future experiments.     

Oxygenated bisabolane fucosides from Carthamus lanatus L

The aerial parts of Carthamus lanatus (Asteraceae) afforded four new oxygenated bisabolane fucosides, 10-hydroperoxy-bisabola-2,11-diene 7-O-beta-D-fucopyranoside, 11-hydro-peroxy-bisabola-2,9-diene 7-O-beta-D-fucopyranoside, 10-hydroxy-bisabola-2,11-diene 7-O-beta-D-fucopyranoside and 11-hydroxy-bisabola-2,9-diene 7-O-beta-D-fucopyranoside together with the known compounds a-bisabolol beta-D-fucopyranoside, asperuloside, sitosterol 3-O-beta-D-glucoside and stigmasterol 3-O-beta-D-glucoside. Asperuloside appears to be the second representative of the iridoid monoterpene group found in the plant family Asteraceae, which until recently was considered to lack iridoids. The main constituent a-bisabolol fucoside exhibited noticeable antibacterial and cytotoxic activities.     

Dynamics of polymorphism of acidocalcisomes in<Emphasis Type="Italic"> Leishmania</Emphasis> parasites

Growth of Leishmania mexicana amazonensis promastigotes in different culture media resulted in structurally and chemically different acidocalcisomes. When grown in SDM-79 medium, the promastigotes showed large spherical acidocalcisomes of up to 1.2 m diameter distributed throughout the cell. X-ray microanalysis and elemental mapping of the organelles showed large amounts of oxygen, phosphorus, sodium, potassium, magnesium, calcium, and zinc. Immunofluorescence microscopy using antisera raised against a peptide sequence of the vacuolar-type proton pyrophosphatase of Arabidopsis thaliana that is conserved in the Leishmania enzyme, indicated localization in acidocalcisomes. When cells were transferred to Warrens medium, the acidocalcisomes transformed from spherical into branched tubular organelles. The labeling pattern of the vacuolar proton-pyrophosphatase, considered as a marker for the organelle, changed accompanying the structural changes of the acidocalcisomes, and the enzyme showed an apparently lower proton-transporting activity when measured in digitonin-permeabilized promastigotes. X-ray microanalysis and elemental mapping of these structures revealed the additional presence of iron. Together, the results reveal that the morphology and composition of acidocalcisomes are greatly influenced by the culture conditions.Electronic Supplementary Material Supplementary material is available in the online version of this article at