Phylogenetic and genetic evidence for base-triples in the catalytic domain of group I introns

Understanding the mechanisms by which ribozymes catalyse chemical reactions requires a detailed knowledge of their structure. The secondary structure of the group I introns has been confirmed by comparison of over 70 published sequences, by chemical protection studies, and by genetic experiments involving compensatory mutations. Phylogenetic data can also be used to identify tertiary interactions in RNA molecules. This was first done by Levitt, who predicted tertiary interactions in transfer RNA, which were subsequently confirmed by X-ray crystallography. More recently, sequence comparison data have been used to predict tertiary interactions in ribosomal RNA. We have searched a complete alignment of the core regions of group I introns for evolutionary covariations that could not be ascribed to classical Watson-Crick or wobble base pairings. Here we describe two examples of phylogenetic covariation that are most simply explained by postulating hydrogen-bonded base-triples similar to those found in tRNA. Genetic experiments with the Tetrahymena and sunY introns confirm the importance of these interactions for the structure of the ribozyme.     

Sur le mycoside Cm,nouveau peptido-glycolipide isolé deMycobacterium marianum

Summary Mycoside C_m, m.p. 198–200° []_D = – 31° (CHCl₃), a new peptido-glycolipid isolated fromMycobacterium marianum, has the approximate molecular formula C₁₀₈H₁₈₅N₇O₂₈ and gives on hydrolysis seven molecules ofd-amino acids (oned-phenylalanine, threed-allo-threonine, threed-alanine), three molecules of 6-deoxyhexoses (one 6-deoxy-talose of as yet undetermined configuration and two molecules of 3,4-di-O-methyl-l-rhamnose); the lipid moiety of mycoside C_m is a hydroxy-acid of approximate formula C₅₀H₉₆O₃; three O-acetyl groups are also present. The preliminary formula (I) is proposed for mycoside C_m.

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60ème communication sur les constitutants des Mycobactéries; 59ème comm. voir: ref. 7.

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Ce travail a bénéficié d'une subvention de la Fondation Waksman pour le développement des Études microbiologiques en France, et d'une subvention du National Institute of Allergy and Infectious Diseases (Grant E 28 38).     

Mixture Model Analysis of Complex Samples

We investigate the effects of a complex sampling design on the estimation of mixture models. An approximate or pseudo likelihood approach is proposed to obtain consistent estimates of class-specific parameters when the sample arises from such a complex design. The effects of ignoring the sample design are demonstrated empirically in the context of an international value segmentation study in which a multinomial mixture model is applied to identify segment-level value rankings. The analysis reveals that ignoring the sample design results in both an incorrect number of segments as identified by information criteria and biased estimates of segment-level parameters.     

Structural basis for the regulation of tubulin by vinblastine

Vinblastine is one of several tubulin-targeting Vinca alkaloids that have been responsible for many chemotherapeutic successes since their introduction in the clinic as antitumour drugs. In contrast with the two other classes of small tubulin-binding molecules (Taxol and colchicine), the binding site of vinblastine is largely unknown and the molecular mechanism of this drug has remained elusive. Here we report the X-ray structure of vinblastine bound to tubulin in a complex with the RB3 protein stathmin-like domain (RB3-SLD). Vinblastine introduces a wedge at the interface of two tubulin molecules and thus interferes with tubulin assembly. Together with electron microscopical and biochemical data, the structure explains vinblastine-induced tubulin self-association into spiral aggregates at the expense of microtubule growth. It also shows that vinblastine and the amino-terminal part of RB3-SLD binding sites share a hydrophobic groove on the alpha-tubulin surface that is located at an intermolecular contact in microtubules. This is an attractive target for drugs designed to perturb microtubule dynamics by interfacial interference, for which tubulin seems ideally suited because of its propensity to self-associate.