162,741 research outputs found
Ancestry and evolution of a secretory pathway serpin
No full textKumar A, Ragg H. Ancestry and evolution of a secretory pathway serpin. BMC Evolutionary Biology. 2008;8(1): 250.Background:The serpin (serine protease inhibitor) superfamily constitutes a class of functionally highly diverse proteins usually encompassing several dozens of paralogs in mammals. Though phylogenetic classification of vertebrate serpins into six groups based on gene organisation is well established, the evolutionary roots beyond the fish/tetrapod split are unresolved. The aim of this study was to elucidate the phylogenetic relationships of serpins involved in surveying the secretory pathway routes against uncontrolled proteolytic activity. Results: Here, rare genomic characters are used to show that orthologs of neuroserpin, a prominent representative of vertebrate group 3 serpin genes, exist in early diverging deuterostomes and probably also in cnidarians, indicating that the origin of a mammalian serpin can be traced back far in the history of eumetazoans. A C-terminal address code assigning association with secretory pathway organelles is present in all neuroserpin orthologs, suggesting that supervision of cellular export/import routes by antiproteolytic serpins is an ancient trait, though subtle functional and compartmental specialisations have developed during their evolution. The results also suggest that massive changes in the exon-intron organisation of serpin genes have occurred along the lineage leading to vertebrate neuroserpin, in contrast with the immediately adjacent PDCD10 gene that is linked to its neighbour at least since divergence of echinoderms. The intron distribution pattern of closely adjacent and co-regulated genes thus may experience quite different fates during evolution of metazoans. Conclusion: This study demonstrates that the analysis of microsynteny and other rare characters can provide insight into the intricate family history of metazoan serpins. Serpins with the capacity to defend the main cellular export/import routes against uncontrolled endogenous and/or foreign proteolytic activity represent an ancient trait in eukaryotes that has been maintained continuously in metazoans though subtle changes affecting function and subcellular location have evolved. It is shown that the intron distribution pattern of neuroserpin gene orthologs has undergone substantial rearrangements during metazoan evolution
Multiple gains of spliceosomal introns in a superfamily of vertebrate protease inhibitor genes
No full textRagg H, Kumar A, Köster K, et al. Multiple gains of spliceosomal introns in a superfamily of vertebrate protease inhibitor genes. BMC Evolutionary Biology. 2009;9(1):208.Background: Intron gains reportedly are very rare during evolution of vertebrates, and the mechanisms underlying their creation are largely unknown. Previous investigations have shown that, during metazoan radiation, the exon-intron patterns of serpin superfamily genes were subject to massive changes, in contrast to many other genes. Results: Here we investigated intron dynamics in the serpin superfamily in lineages pre- and postdating the split of vertebrates. Multiple intron gains were detected in a group of ray-finned fishes, once the canonical groups of vertebrate serpins had been established. In two genes, cooccurrence of non-standard introns was observed, implying that intron gains in vertebrates may even happen concomitantly or in a rapidly consecutive manner. DNA breakage/repair processes associated with genome compaction are introduced as a novel factor potentially favoring intron gain, since all non-canonical introns were found in a lineage of ray-finned fishes that experienced genomic downsizing. Conclusion: Multiple intron acquisitions were identified in serpin genes of a lineage of ray-finned fishes, but not in any other vertebrates, suggesting that insertion rates for introns may be episodically increased. The co-occurrence of non-standard introns within the same gene discloses the possibility that introns may be gained simultaneously. The sequences flanking the intron insertion points correspond to the proto-splice site consensus sequence MAG↑N, previously proposed to serve as intron insertion site. The association of intron gains in the serpin superfamily with a group of fishes that underwent genome compaction may indicate that DNA breakage/repair processes might foster intron birth
Messenger RNA coding for phenylalanine ammonia-lyase: Characterization and partial purification from cell suspension cultures of Petroselinum hortense
No full textRagg H, Hahlbrock K. Messenger RNA coding for phenylalanine ammonia-lyase: Characterization and partial purification from cell suspension cultures of Petroselinum hortense. Eur. J. Biochem. 1980;103:323-330
Structure and expression of the gene coding for the human serpin hLS2
No full textRagg H, Preibisch G. Structure and expression of the gene coding for the human serpin hLS2. J. Biol. Chem. 1988;263:12129-12134
On the activation of human leuserpin-2, a thrombin inhibitor, by glycosaminoglycans
No full textRagg H, Ulshöfer T, Gerewitz J. On the activation of human leuserpin-2, a thrombin inhibitor, by glycosaminoglycans. J. Biol. Chem. 1990;265:5211-5218
Glycosaminoglycan-mediated leuserpin-2/thrombin interaction: structure-function relationships
No full textRagg H, Ulshöfer T, Gerewitz J. Glycosaminoglycan-mediated leuserpin-2/thrombin interaction: structure-function relationships. J. Biol. Chem. 1990;265:22386-22301
Coordinated regulation of 4-coumarate: CoA ligase and phenylalanine ammonia-lyase mRNAs in cultured plant cells
No full textRagg H, Kuhn DN, Hahlbrock K. Coordinated regulation of 4-coumarate: CoA ligase and phenylalanine ammonia-lyase mRNAs in cultured plant cells. J. Biol. Chem. 1981;256:10061-10065
Translation of poly(A)-containing and poly(A)-free messenger RNA for phenylalanine ammonia-lyase, a plant-specific protein, in a reticulocyte lysate
No full textRagg H, Schröder J, Hahlbrock K. Translation of poly(A)-containing and poly(A)-free messenger RNA for phenylalanine ammonia-lyase, a plant-specific protein, in a reticulocyte lysate. Biochim. Biophys. Acta. 1977;474:226-233
Poly(A)-containing RNA from Petroselinum hortense: Isolation, properties and messenger function in vitro
No full textRagg H, Schröder J, Hahlbrock K. Poly(A)-containing RNA from Petroselinum hortense: Isolation, properties and messenger function in vitro. Molecular Biology Reports. 1975;2:119-127
Human peptidylglycine alpha-amidating monooxygenase: cDNA cloning and functional expression of a truncated form in COS cells
No full textGlauder J, Ragg H, Rauch J, Engels JW. Human peptidylglycine alpha-amidating monooxygenase: cDNA cloning and functional expression of a truncated form in COS cells. Biochem. Biophys. Res. Commun. 1990;169:551-558
- …
