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Karin Julenius

Publications and source records attributed to Karin Julenius.

4 recordsLinked to original sources
PubMed2006

Protein evolution is faster outside the cell.

Some proteins are highly conserved across all species, whereas others diverge significantly even between closely related species. Attempts have been made to correlate the rate of protein evolution to amino acid composition, protein dispensability, and the number of protein-protein interactions, but in all cases, conflicting studies have shown that the theories are hard to confirm experimentally. The only correlation that is undisputed so far is that highly/broadly expressed proteins seem to evolve at a lower rate. Consequently, it has been suggested that correlations between evolution rate and factors like protein dispensability or the number of protein-protein interactions could be just secondary effects due to differences in expression. The purpose of this study was to analyze mammalian proteins/genes with known subcellular location for variations in evolution rates. We show that proteins that are exported (extracellular proteins) evolve faster than proteins that reside inside the cell (intracellular proteins). We find weak, but significant, correlations between evolution rates and expression levels, percentage of tissues in which the proteins are expressed (expression broadness), and the number of protein interaction partners. More important, we show that the observed difference in evolution rate between extra- and intracellular proteins is largely independent of expression levels, expression broadness, and the number of protein-protein interactions. We also find that the difference is not caused by an overrepresentation of immunological proteins or disulfide bridge-containing proteins among the extracellular data set. We conclude that the subcellular location of a mammalian protein has a larger effect on its evolution rate than any of the other factors studied in this paper, including expression levels/patterns. We observe a difference in evolution rates between extracellular and intracellular proteins for a yeast data set as well and again show that it is completely independent of expression levels.

Amino Acid Sequence↗
PubMed2004

Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites.

O-GalNAc-glycosylation is one of the main types of glycosylation in mammalian cells. No consensus recognition sequence for the O-glycosyltransferases is known, making prediction methods necessary to bridge the gap between the large number of known protein sequences and the small number of proteins experimentally investigated with regard to glycosylation status. From O-GLYCBASE a total of 86 mammalian proteins experimentally investigated for in vivo O-GalNAc sites were extracted. Mammalian protein homolog comparisons showed that a glycosylated serine or threonine is less likely to be precisely conserved than a nonglycosylated one. The Protein Data Bank was analyzed for structural information, and 12 glycosylated structures were obtained. All positive sites were found in coil or turn regions. A method for predicting the location for mucin-type glycosylation sites was trained using a neural network approach. The best overall network used as input amino acid composition, averaged surface accessibility predictions together with substitution matrix profile encoding of the sequence. To improve prediction on isolated (single) sites, networks were trained on isolated sites only. The final method combines predictions from the best overall network and the best isolated site network; this prediction method correctly predicted 76% of the glycosylated residues and 93% of the nonglycosylated residues. NetOGlyc 3.1 can predict sites for completely new proteins without losing its performance. The fact that the sites could be predicted from averaged properties together with the fact that glycosylation sites are not precisely conserved indicates that mucin-type glycosylation in most cases is a bulk property and not a very site-specific one. NetOGlyc 3.1 is made available at www.cbs.dtu.dk/services/netoglyc.

Algorithms↗
PubMed2002

Coupling of ligand binding and dimerization of helix-loop-helix peptides: spectroscopic and sedimentation analyses of calbindin D9k EF-hands.

Isolated Ca2+-binding EF-hand peptides have a tendency to dimerize. This study is an attempt to account for the coupled equilibria of Ca2+-binding and peptide association for two EF-hands with strikingly different loop sequence and net charge. We have studied each of the two separate EF-hand fragments from calbindin D9k. A series of Ca2+-titrations at different peptide concentrations were monitored by CD and fluorescence spectroscopy. All data were fitted simultaneously to both a complete model of all possible equilibrium intermediates and a reduced model not including dimerization in the absence of Ca2+. Analytical ultracentrifugation shows that the peptides may occur as monomers or dimers depending on the solution conditions. Our results show strikingly different behavior for the two EF-hands. The fragment containing the N-terminal EF-hand shows a strong tendency to dimerize in the Ca2+-bound state. The average Ca2+-affinity is 3.5 orders of magnitude lower than for the intact protein. We observe a large apparent cooperativity of Ca2+ binding for the overall process from Ca2+-free monomer to fully loaded dimer, showing that a Ca2+-free EF-hand folds upon dimerization to a Ca2+-bound EF-hand, thereby presenting a preformed binding site to the second Ca2+-ion. The C-terminal EF-hand shows a much smaller tendency to dimerize, which may be related to its larger net negative charge. In spite of the differences in dimerization behavior, the Ca2+ affinities of both EF-hand fragments are similar and in the range lgK = 4.6-5.3.

Amino Acid Sequence↗