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Peroxisomes are organelles with vital functions in metabolism and their dysfunction is associated with human diseases. To fulfill their multiple roles, peroxisomes import nuclear-encoded matrix proteins, most carrying a peroxisomal targeting signal (PTS) 1. The receptor Pex5p recruits PTS1-proteins for import into peroxisomes; whether and how this process is posttranslationally regulated is unknown. Here, we identify 22 phosphorylation sites of Pex5p. Yeast cells expressing phospho-mimicking Pex5p-S507/523D (Pex5p2D) show decreased import of GFP with a PTS1. We show that the binding affinity between a PTS1-protein and Pex5p2D is reduced. An in vivo analysis of the effect of the phospho-mimicking mutant on PTS1-proteins revealed that import of most, but not all, cargos is affected. The physiological effect of the phosphomimetic mutations correlates with the binding affinity of the corresponding extended PTS1-sequences. Thus, we report a novel Pex5p phosphorylation-dependent mechanism for regulating PTS1-protein import into peroxisomes. In a broader view, this suggests that posttranslational modifications can function in fine-tuning the peroxisomal protein composition and, thus, cellular metabolism. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tibs.2008.09.009 Byline: Nikos Pinotsis (1)(2), Patrizia Abrusci (3), Kristina DjinoviA-Carugo (3)(4), Matthias Wilmanns (1) Abstract: The contraction-relaxation cycle of muscle cells translates into large movements of several filament systems in sarcomeres, requiring special molecular mechanisms to maintain their structural integrity. Recent structural and functional data from three filaments harboring extensive arrays of immunoglobulin-like domains - titin, filamin and myomesin - have, for the first time, unraveled a common function of their terminal domains: assembly and anchoring of the respective filaments. In each case, the protein-protein interactions are mediated by antiparallel dimerization modules via intermolecular [beta]-sheets. These observations on terminal filament assembly indicate an attractive model for several other filament proteins that require structural characterization. Author Affiliation: (1) European Molecular Biology Laboratory Hamburg, Notkestrasse 85, D-22603 Hamburg, Germany (2) Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK (3) Department for Biomolecular Structural Chemistry, Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria (4) Department of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, AA kerAeva 5, 1000 Ljubljana, Slovenia

The structure solution, model building and refinement of a biologically important second SH3 (Src homology -3) domain of ponsin are described by using high-angular-resolution powder diffraction. The results have shown the power and future applicability of the powder technique in structural biology.

Author(s): Peijian Zou [1, 6]; Nikos Pinotsis [1, 2, 6]; Stephan Lange [3, 4]; Young-Hwa Song [1]; Alexander Popov [1]; Irene Mavridis [2]; Olga M. Mayans [1, 5]; Mathias Gautel [...]

Anthrax caused by Bacillus anthracis represents a major bioterroristic threat. B. anthracis produces lethal toxin (LeTx), a combination of lethal factor (LF) and protective antigen that plays a major role in anthrax pathogenesis. We demonstrate that human neutrophil ~-defensins are potent inhibitors of LF. The inhibition of LF by human neutrophil protein (HNP-1) was noncompetitive. HNP-1 inhibited cleavage of a mitogen-activated protein kinase kinase and restored impaired mitogen-activated protein kinase signaling in LeTx-treated macrophages. HNP-1 rescued murine macrophages from B. anthracis-induced cytotoxicity, and in vivo treatment with HNP-1-3 protected mice against the fatal consequences of LeTx. defensin | innate immunity | Bacillus anthracis

Research reveals that during embryogenesis recruitment of the transcriptional coactivator OBF-1 is mediated by the POU dimer of the PORE, whereas the concensus MORE does not participate. Data point out that the specificity of the POU dimer assemblies recognize distinct transcriptional readouts.

Connectin, or titin, is a giant muscle protein which is important for spatial and temporal control of sarcomeres found in striated muscle. Titin kinase is the only catalytic domain of titin, and its crystal structure shows the way in which a tyrosine inhibits the active site. This tyrosine appears to be a binding partner of the substrate of titin kinase. The research shows that the titin kinase may be important in myofibrillogenesis.

An engineered dinuclear copper center was used to describe the crystal structures of wild-type and mutant subunit II (CyoA) from the Escherichia coli respiratory quinol oxidase complex. Wild-type and mutant CyoA were studied at 2.5-Angstrom and 2.3-Angstrom resolution, respectively. The results revealed that the dinuclear copper center is inserted between strands beta5 and beta6 and beta9 and beta10, with a distance of 2.5-Angstrom in between the two coppers. It is surrounded by residues consisting of cytochrome c and quinol oxidases.