Structure and assembly of the 20S proteasome

The barrel-shaped 20S proteasome is one of the two components of a larger 26S particle, the multicatalytic 2000-kDa protease complex. The proteolytic sites are located in the inner chamber of the 20S particle and are only accessible via narrow entrances. This paper reviews the current knowledge concerning proteasome formation, proteolytic activities, structural aspects and assembly. Eukaryotic proteasomes are made up by four rings each of which contains seven different subunits occurring at fixed positions. While the outer rings contain α-type subunits, the inner ones comprise β-type subunits. The current assembly model for eukaryotic 20S proteasomes is based upon the detection of 13S and 16S intermediates, respectively, in addition to previous findings with archaebacterial and eubacterial proteasome assembly. The available data suggest a cooperative assembly of the α-type and β-type subunits into half proteasome-like complexes followed by dimerization into proteasomes. During or after dimerization of half proteasomes, the β-type subunits are processed. The prosequence of the β-type subunits is essential for the assembly process and prevents protease activity of immature proteasomes.     

On the decrement function of an action potential in a volume conductor

Zusammenfassung Eine Modifikation der Feldgleichung vonLorente de Nó wird einer Fourier-Transformation unterworfen. Dabei zeigt sich, dass das Dekrement einer jeden Frequenz eineK ₀-Funktion in ihrem eigenen Maßstab darstellt. Die theoretische Dekrementkurve stimmt gut mit der experimentell ausgearbeiteten überein.     

The role of the proteasome in the generation of MHC class I ligands and immune responses

The ubiquitin–proteasome system (UPS) degrades intracellular proteins into peptide fragments that can be presented by major histocompatibility complex (MHC) class I molecules. While the UPS is functional in all mammalian cells, its subunit composition differs depending on cell type and stimuli received. Thus, cells of the hematopoietic lineage and cells exposed to (pro)inflammatory cytokines express three proteasome immunosubunits, which form the catalytic centers of immunoproteasomes, and the proteasome activator PA28. Cortical thymic epithelial cells express a thymus-specific proteasome subunit that induces the assembly of thymoproteasomes. We here review new developments regarding the role of these different proteasome components in MHC class I antigen processing, T cell repertoire selection and CD8 T cell responses. We further discuss recently discovered functions of proteasomes in peptide splicing, lymphocyte survival and the regulation of cytokine production and inflammatory responses.     

Distribution and variation of a collagen-degrading enzyme in the uterus of pregnant rats

Zusammenfassung Extrakte aus Uteruswand und Glandula myometralis bauen bei saurem pH Kollagen ab. Die Drüsen haben eine grössere spez. Aktivität. Doch zeigt das Uterusenzym eine grössere Affinität zum Substrat, und seine Gesamtaktivität überwiegt post partum.

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This work was done with the support of the Muscular Dystrophy Association of America to Prof.F. Verzár.     

The origin of the action potential in frog stomach muscle and heart

Zusammenfassung Das Aktionspotential von Herz- und Magenmuskulatur des Frosches scheint nicht vom Einund Ausstoss der Ionen, sondern vom elektronischen Aufbau der Zellmembran abhängig zu sein.     

The effect of pancreozymin and acetylcholine on the membrane potential of the pancreatic acinar cells

Zusammenfassung Acetylcholin und Pancreozymin induzieren beide eine Depolarisation der Azinuszellmembran in der Bauchspeicheldrüse. Nur die Wirkung von Acetylcholin wird von Atropin blockiert. Das Ruhepotential kann auch durch eine erhöhte Kaliumkonzentration im Extrazellularraum reduziert werden, diese Wirkung wird nicht von Atropin beeinflusst. Die Acetylcholin-induzierte Depolarisation ist nicht von extrazellularer Kalziumkonzentration abhängig, sondern ist wahrscheinlich eine notwendige Bedingung für den Sekretionsprozess.

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Supported by grants from The Carlsberg Foundation, The Wellcome Trust and I. and H. Weismann's legat. Present address: Inst. Med. Physiol. C, Univ. Copenhagen, Denmark.

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Cholecystokinin-Pancreozymin was kindly provided by GIH research unit, Chemistry Department, Karolinska Institutet, Stockholm.     

The morphology of the Schwann cells and the unmyelinated fibers of a nerve supplying an immobilized muscle

Summary Hind limbs of cats were immobilized in the resting position for varying periods and the nerve supplying the medial head of the gastrocnemius muscle was studied while it was undergoing immobilization atrophy. Degenerative changes in the unmyelinated fibers and the Schwann, cells, followed by an abundant increase in collagen, were noticed after prolonged immobilization. Electron microscopic evidence that Schwann cells produce the collagen is discussed.     

The effect of catecholamines and nicotine on the transmembranal potential of frog liver cells

Resumen La adrenalina (0.1 a 0.5 mg/rana) hiperpolarizó los hepatocitos deR. pipiens y depolarizó a dosis mas altas. El inhibidor de la monoamino oxidasa pargilina (100 mg/kg, 24–48 h antes) impidió este efecto.     

The effects of hydrocortisone and glycyrrhizine on the enzyme releases of arylsulfatase and hyaluronidase from lysosomes of liver

Summary Hydrocortisone and glycyrrhizine act as both stabilizers and labilizers of the lysosomes of liver. The effect of both agents on the lysosomes is changeable according to the duration of their administration.     

The effects of hydrocortisone and glycyrrhizine on the enzyme releases of arylsulfatase and hyaluronidase from lysosomes of liver

Hydrocortisone and glycyrrhizine act as both stabilizers and labilizers of the lysosomes of liver. The effect of both agents on the lysosomes is changeable according to the duration of their administration.     

The action of cycloheximide on the action potential and protein synthesis in medullatedXenopus axons

Summary Cycloheximide depresses maximum rate of change in membrane potential observed during the rising phase of the action potential in single medullated axons ofXenopus. Time course of depression is independent of cycloheximide concentration over a range that almost completely inhibits leucine incorporation into axonal proteins.     

The role of vitamin E in preventing the hemolysis of kid and chick erythrocytes with Tween 20

Summary Erythrocytes of vitamin E-deficient kids and chicks were hemolyzed at concentrations of Tween 20 above 1%. In vivo or in vitro uptake of vitamin E by the erythrocytes, or the addition of dithiothreitol or 2-mercaptoethanol, prevented the hemolysis with Tween 20.     

Elucidation of the relationship between enzyme activity and internal motion using a lysozyme stabilized by cavity-filling mutations

We investigated the activity and the internal motions of a stabilized mutant hen lysozyme (HEL) in which the residues M12 and L56 were mutated to L and F, respectively (LF mutant HEL). The result of the activity measurements against glycol chitin at various temperatures suggested that the temperature dependence of the activity of LF mutant HEL shifted to the high-temperature side compared with that of wild-type HEL. The detailed internal motions of LF mutant HEL in the absence and presence of a substrate analogue, (NAG)₃, were examined by model-free analysis at 35°C. The results showed that the internal motions of LF mutant HEL in the presence of (NAG)₃ were drastically restricted compared with those in wild-type HEL. Our findings thus suggested that the mutation to the stabilized lysozyme restricted internal motions required for the enzymatic reaction.Received 8 February 2005; accepted 10 March 2005Y. Yoshida and T. Ohkuri contributed equally to this work.