Zinc in the Biosciences (online collection published by Metallomics)

The Metallomics Zinc in the biosciences online collection has now been updated and expanded to include additional reports in this field.

The original list was composed of articles published in a themed issue of Metallomics (6, 2014, guest edited by Prof. Wolfgang Maret) that highlighted emerging high-impact areas of zinc in the biosciences.  Since then, this collection has expanded and will continue to grow to include additional reports in this field, covering various aspects of this important area of metal biology.

New articles will be added to this collection as they are published. For information about the scope of the journal please visit the Metallomics about the journal page.

New publication supported by the Zinc-net COST Action!

Aberrant zinc binding to immature conformers of metal-free copper–zinc superoxide dismutase triggers amorphous aggregation-

Sónia S. Leal, Joana S. Cristóvão, Antje Biesemeier, Isabel Cardoso and Cláudio M. Gomes.

Here the Abstract:

Superoxide dismutase 1 (SOD1) is a Cu/Zn metalloenzyme that aggregates in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. Correct metal insertion during SOD1 biosynthesis is critical to prevent misfolding; however Zn2+ can bind to the copper-site leading to an aberrantly metallated protein. These effects of Zn2+ misligation on SOD1 aggregation remain to be explored, even though Zn2+ levels are upregulated in ALS motor neurons. Here we use complementary biophysical methods to investigate Zn2+ binding and its effects on the aggregation of three immature metal-free SOD1 conformers that represent biogenesis intermediates: dimeric, monomeric and reduced monomeric SOD1. Using isothermal titration calorimetry we determined that Zn2+ binds to all conformers both at the zinc- as well as to the copper-site; however Zn2+ binding mechanisms to the zinc-site have distinct characteristics across immature conformers. We show that this ‘zinc overload’ of immature SOD1 promotes intermolecular interactions, as evidenced by dynamic light scattering and ThT fluorescence kinetic studies. Analysis of aged zinc-induced aggregates by energy-dispersive X-ray and electron energy-loss spectroscopy shows that aggregates integrate some Zn2+. In addition, electron diffraction analysis identifies nano-scaled crystalline materials and amyloid fibril-like reflections. Transmission electron microscopy reveals that Zn2+ diverts the SOD1 aggregation pathway from fibrils to amorphous aggregate, and electrophoretic analysis evidences an increase in insoluble materials. Overall, we provide evidence that aberrant zinc coordination to immature conformers broadens the population of SOD1 misfolded species at early aggregation stages and provide evidence for a high structural polymorphism and heterogeneity of SOD1 aggregates.

For the full story on Metallomics, click HERE.

LiZIP3 mediates the tightly regulated zinc import in Leishmania infantum parasites

Ne publication from Sandra Carvalho in Molecular Microbiology.


Cellular zinc homeostasis ensures that the intracellular concentration of this element is kept within limits that enable its participation in critical physiological processes without exerting toxic effects. We report here the identification and characterization of the first mediator of zinc homeostasis in Leishmania infantum, LiZIP3, a member of the ZIP family of divalent metal-ion transporters. The zinc transporter activity of LiZIP3 was first disclosed by its capacity to rescue the growth of Saccharomyces cerevisiae strains deficient in zinc acquisition. Subsequent expression of LiZIP3 in Xenopus laevis oocytes was shown to stimulate the uptake of a broad range of metal ions, among which Zn2+ was the preferred LiZIP3 substrate (K0.5 ≈ 0.1 μM). Evidence that LiZIP3 functions as a zinc importer in L. infantum came from the observations that the protein locates to the cell membrane and that its overexpression leads to augmented zinc internalization. Importantly, expression and cell-surface location of LiZIP3 are lost when parasites face high zinc bioavailability. LiZIP3 decline in response to zinc is regulated at the mRNA level in a process involving (a) short-lived protein(s). Collectively, our data reveal that LiZIP3 enables L. infantum to acquire zinc in a highly regulated manner, hence contributing to zinc homeostasis.

The article can be found HERE.