Dynamic personalities of proteins

Because proteins are central to cellular function, researchers have sought to uncover the secrets of how these complex macromolecules execute such a fascinating variety of functions. Although static structures are known for many proteins, the functions of proteins are governed ultimately by their dynamic character (or 'personality'). The dream is to 'watch' proteins in action in real time at atomic resolution. This requires addition of a fourth dimension, time, to structural biology so that the positions in space and time of all atoms in a protein can be described in detail.     

Cytological demonstration of female heterogamety in isopods

Résumé Des chromosomes sexuels, inconnus jusqu'à présent chez les Isopodes, ont été trouvés dans 4 espèces de la superespèceJaera marina (Janiridae, Asellota). Il s'agit d'un système multiple de chromosomes sexuels, ce qui aboutit à la formation d'un trivalent sexuel dans la méiose femelle. Les femelles — hétérogamétiques — ont la constitution XY₁Y₂, les mâles étant XX. D'après les données chromosomiques présentées par les 4 espèces étudiées, la formation du système multiple sexuel est due à des processus cytologiques évolutifs d'ordre Robertsonien.

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Aided by a grant from the Janggen Pöhn Foundation (St. Gallen, Switzerland) and supported by the Swiss Commission for the Biological Station of Roscoff.     

Light-microscopic demonstration of drug-induced myelin bodies in the liver of rats

Zusammenfassung Sekundäre Lysosomen mit multilamellärer Myelinkörper-Struktur, die in der Rattenleber nach Behandlung mit verschiedenen Agenzien (z.B. Triparanol, Chloroquin, Mepacrin) induziert werden können, sind aufgrund ihrer Malteserkreuz-Konfiguration im polarisierten Licht lichtmikroskopisch nachweisbar. Mit fluoreszierenden Substanzen (Chloroquin, Mepacrin) zeigen die Malteserkreuz-Einschlüsse im Zytoplasma starke Fluoreszenz, was auf ihre Akkumulation in den Myelinkörpern hinweist. Nach längerer Behandlung treten Myelinkörper auch in zahlreichen andern Organen auf und induzieren unter anderem die Bildung von Schaumzellen in der Lunge.     

Intrinsic dynamics of an enzyme underlies catalysis

A unique feature of chemical catalysis mediated by enzymes is that the catalytically reactive atoms are embedded within a folded protein. Although current understanding of enzyme function has been focused on the chemical reactions and static three-dimensional structures, the dynamic nature of proteins has been proposed to have a function in catalysis. The concept of conformational substates has been described; however, the challenge is to unravel the intimate linkage between protein flexibility and enzymatic function. Here we show that the intrinsic plasticity of the protein is a key characteristic of catalysis. The dynamics of the prolyl cis-trans isomerase cyclophilin A (CypA) in its substrate-free state and during catalysis were characterized with NMR relaxation experiments. The characteristic enzyme motions detected during catalysis are already present in the free enzyme with frequencies corresponding to the catalytic turnover rates. This correlation suggests that the protein motions necessary for catalysis are an intrinsic property of the enzyme and may even limit the overall turnover rate. Motion is localized not only to the active site but also to a wider dynamic network. Whereas coupled networks in proteins have been proposed previously, we experimentally measured the collective nature of motions with the use of mutant forms of CypA. We propose that the pre-existence of collective dynamics in enzymes before catalysis is a common feature of biocatalysts and that proteins have evolved under synergistic pressure between structure and dynamics.