Azotobacter vinelandii scaffold protein NifU transfers iron to NifQ as part of the iron-molybdenum cofactor biosynthesis pathway for nitrogenase

ABSTRACTAzotobacter vinelandii molybdenum-dependent nitrogenase obtains molybdenum from NifQ, a monomeric iron-sulfur molybdoprotein. This protein requires of a preexisting [Fe-S] cluster to form a [MoFe3S4] group to serve as specific donor during nitrogenase cofactor biosynthesis. Here, we show biochemical evidence for NifU being the donor of the [Fe-S] cluster. Protein-protein interaction studies using apo-NifQ and as-isolated NifU demonstrated the interaction between both proteins which is only effective when NifQ is unoccupied by its [Fe-S] cluster. The apo-NifQ iron content increased after the incubation with as-isolated NifU, reaching similar levels to holo-NifQ after the interaction between apo-NifQ and NifU with reconstituted transient [Fe4-S4] groups. These results also indicate the necessity of co-expressing NifU together with NifQ in the pathway to provide molybdenum for the biosynthesis of nitrogenase in engineered nitrogen-fixing plants.

SLC66 Lysosomal amino acid transporters in GtoPdb v.2021.2

This is a family of 5 evolutionarily related proteins. Their structural similarities suggest that they are transporters. Biochemical evidence supports transporter activity for SLC66A1 (LAAT1) and SLC66A4 (CTNS; Cystinosin). The functions of the 3 remaining members of the family are undetermined.

Are Nemiana Palij and Beltanelliformis Menner (Beltanelloides (Sokolov)) synonyms or different genera?

During recent decades, the issue of the nature of Ediacaran cyclic imprints, including the widely distributed in Podillia (southwestern Ukraine) Nemiana simplex Palij, 1976, and the less common Beltanelliformis brunsae Menner, 1974 (Beltanelloides sorichevae (Sokolov), 1965) has been actively debated. Several new and similar forms were discovered in other regions of the Globe. The disk-like outlines were considered to be sufficient characters to synonymize several earlier recognized genera and species. The main additional features used to distinguish cyclic genera included such features as the shape and sculpture of surfaces, facial differences, and geological age. Novel palaeobiochemical studies of these ancient remains opened a new phase of discussions on the possible identities of the organisms that formed these fossil structures. Sometimes the remains are covered with thin brown films providing biochemical evidence for the cyanobacterial nature of some structures, for example Beltanelliformis brunsae. However, these films are found only in clayey or carbonate environments (rocks). For Nemiana Palij, characteristic features are clustered communities and budding. In contrast, Beltanelliformis brunsae formed taphonomic communities of closely arranged disks almost identical in their shape and size. Nemiana simplex structures are confined to clastic rocks (mostly thin-grained sandstones or siltstone), which are not suitable for good preservation of imprints and organic remains of ancient animals, cyanobacteria, algae, and plants. Considering these and some additional considerations, synonimization of Nemiana та Beltanelliformis, as well as some other Ediacaran fossil structures differing in their morphology, is at best premature.

Morphology, clearing efficacy, and mTOR dependency of the organelle autophagoproteasome

The interplay between autophagy (ATG) and ubiquitin proteasome (UP) cell-clearing systems was recently evidenced at biochemical and morphological levels, where subunits belonging to both pathways co-localize within a novel organelle named autophagoproteasome (APP). We previously documented that APP occurs at baseline conditions, while it is hindered by neurotoxicant administration. This is bound to the activity of the mechanistic target of rapamycin (mTOR), since APP is stimulated by mTOR inhibition, which in turn, is correlated with cell protection. In this brief report, we provide novel, morphological and biochemical evidence on APP, suggesting the presence of active UP subunits within ATG vacuoles. Although a stream of interpretation considers such a merging as a catabolic pathway to clear inactive UP subunits, our data further indicate that UP-ATG merging may rather provide an empowered catalytic organelle.

Cabergoline reduces 3-methoxytyramine in a SDHC patient with metastatic paraganglioma and prolactinoma

Summary We observed a novel therapeutic response with cabergoline in a male patient with a dopamine-secreting head and neck paraganglioma (HNPGL), macroprolactinoma and germline succinate dehydrogenase C mutation (SDHC). The macroprolactinoma was treated with cabergoline which gave an excellent response. He was found to have raised plasma 3-methoxytyramine of 1014 pmol/L (NR: 0–180 pmol/L); but it was unclear if this was a drug-induced phenomenon from dopamine agonist (DA) therapy. Cabergoline was stopped for 4 weeks and the 3-methoxytyramine level increased significantly to 2185 pmol/L, suggesting a biochemical response of his HNPGL. Subsequently, Gallium-68 Dotatate PET and MRI (Gallium-68 Dotatate PET/MRI) demonstrated a second lesion in the sacrum. Both the HNPGL and metastatic sacral deposit received external beam radiotherapy with a good biochemical and radiological response. Conclusion Our case report highlights the rare potential of germline SDHC mutations causing metastatic paraganglioma and concurrent pituitary tumours. Cabergoline treatment may lower elevated 3-methoxytyramine levels and, therefore, mask the biochemical evidence of metastatic disease but also may have therapeutic relevance in dopamine-secreting pheochromocytomas/paragangliomas (PPGLs). Learning points Several neuroendocrine tumours (NETs) express dopamine D2 and D4 receptors. In this case report, cabergoline significantly reduced plasma 3-methoxytyramine level in a patient with functional HNPGL. Cabergoline might have therapeutic relevance in dopamine-secreting PPGLs. Paragangliomas associated with SDHC mutation classically present with asymptomatic non-functional HNPGL and have rare metastatic potential. The association of pheochromocytoma or paraganglioma and pituitary adenoma is now a well-described rare association (<1%), designated as the three P association. While the three P association is most commonly seen with succinate dehydrogenase B and D mutations, it has also been described in patients with SDHA and SDHC mutations. Cabergoline treatment may lower elevated 3-methoxytyramine levels and mask the biochemical evidence of metastatic disease. Regular functional imaging with Gallium-68 Dotatate PET/MRI provides better evidence of metastatic disease.