Restricted N-glycan Conformational Space in the PDB and Its Implication in Glycan Structure Modeling

Understanding glycan structure and dynamics is central to understanding protein-carbohydrate recognition and its role in protein-protein interactions. Given the difficulties in obtaining the glycan''s crystal structure in glycoconjugates due to its flexibility and heterogeneity, computational modeling could play an important role in providing glycosylated protein structure models. To address if glycan structures available in the PDB can be used as templates or fragments for glycan modeling, we present a survey of the N-glycan structures of 35 different sequences in the PDB. Our statistical analysis shows that the N-glycan structures found on homologous glycoproteins are significantly conserved compared to the random background, suggesting that N-glycan chains can be confidently modeled with template glycan structures whose parent glycoproteins share sequence similarity. On the other hand, N-glycan structures found on non-homologous glycoproteins do not show significant global structural similarity. Nonetheless, the internal substructures of these N-glycans, particularly, the substructures that are closer to the protein, show significantly similar structures, suggesting that such substructures can be used as fragments in glycan modeling. Increased interactions with protein might be responsible for the restricted conformational space of N-glycan chains. Our results suggest that structure prediction/modeling of N-glycans of glycoconjugates using structure database could be effective and different modeling approaches would be needed depending on the availability of template structures.     

Induction of globin mRNA expression by interleukin-3 in a stem cell factor-dependent SV-40 T-antigen-immortalized multipotent hematopoietic cell line

Erythropoiesis requires the stepwise action on immature progenitors of several growth factors, including stem cell factor (SCF), interleukin 3 (IL-3), and erythropoietin (Epo). Epo is required to sustain proliferation and survival of committed progenitors and might further modulate the level of expression of several erythroid genes, including globin genes. Here we report a new SCF-dependent immortalized mouse progenitor cell line (GATA-1 ts SCF) that can also grow in either Epo or IL-3 as the sole growth factor. When grown in SCF, these cells show an "open" chromatin structure of the beta-globin LCR, but do not significantly express globin. However, Epo or IL-3 induce globin expression and are required for its maintainance. This effect of IL-3 is unexpected as IL-3 was previously reported either to be unable to induce hemoglobinization, or even to antagonize it. This suggests that GATA-1 ts SCF cells may have progressed to a stage in which globin genes are already poised for expression and only require signal(s) that can be elicited by either Epo or IL-3. Through the use of inhibitors, we suggest that p38 may be one of the molecules modulating induction and maintenance of globin expression.     

A new syndrome in the group of euhidrotic ectodermal dysplasia

Summary A new form of ectodermal dysplasia was observed in two siblings, offspring of healthy non-consanguineous parents. The main findings in both children are: hypodontia, abnormally shaped teeth, scalp hypotrichosis, pili annulati, follicular hyperkeratosis on the trunk and limbs, intensified delineation and reticular hyperpigmentation of the nape, and hyperopia; one of the siblings also has astigmatism. As both patients have normal nails and are euhidrotic, this is an ectodermal dysplasia of the pilodental subgroup. The cause is probably genetic and autosomal-recessive inheritance is most likely.     

Allometric and nonallometric components of Drosophila wing shape respond differently to developmental temperature

Phenotypic plasticity of wing size and shape of Drosophila simulans was analyzed across the entire range of viable developmental temperatures with Procrustes geometric morphometric method. In agreement with previous studies, size clearly decreases when temperature increases. Wing shape variation was decomposed into its allometric (24%) and nonallometric (76%) components, and both were shown to involve landmarks located throughout the entire wing blade. The allometric component basically revealed a progressive, monotonous variation along the temperature. Surprisingly, nonallometric shape changes were highly similar at both extremes of the thermal range, suggesting that stress, rather than temperature per se, is the key developmental factor affecting wing shape.     

Single-cell determination of iron content in magnetotactic bacteria: implications for the iron biogeochemical cycle

Magnetotactic bacteria (MTB) are ubiquitous aquatic microorganisms that mineralize dissolved iron into intracellular magnetic crystals. After cell death, these crystals are trapped into sediments that remove iron from the soluble pool. MTB may significantly impact the iron biogeochemical cycle, especially in the ocean where dissolved iron limits nitrogen fixation and primary productivity. A thorough assessment of their impact has been hampered by a lack of methodology to measure the amount of, and variability in, their intracellular iron content. We quantified the iron mass contained in single MTB cells of Magnetospirillum magneticum strain AMB-1 using a time-resolved inductively coupled plasma-mass spectrometry methodology. Bacterial iron content depends on the external iron concentration, and reaches a maximum value of ~10⁻⁶ ng of iron per cell. From these results, we calculated the flux of dissolved iron incorporation into environmental MTB populations and conclude that MTB may mineralize a significant fraction of dissolved iron into crystals.     

A Systematic Approach for the Genetic Dissection of Protein Complexes in Living Cells

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