Zinc in the Biosciences

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Abstract

Editorial for Metallomics Themed Issue: Zinc in the Biosciences.

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Many years ago, I saw someone wearing a T-shirt embroidered with the message: I zinc, therefore I am. The transliteration of the word “think” was meant to draw attention to the role of zinc in memory formation in the human brain. Zinc is important for cellular functions in all organ systems. Its global roles are unlike those of any other transition metal ion and more similar to those of magnesium and calcium ions. In fact, zinc extends the roles of redox-inert metals such that they cover together more than six orders of magnitude of concentrations, from millimolar to picomolar, for possible biological control. Zinc(II) ions are involved in intra- and intercellular signalling at remarkably low concentrations. These regulatory functions add to the already impressive catalytic and structural roles of zinc in about 3000 proteins, 10% of all human proteins. Without zinc, the conformational space of proteins would be much smaller. Zinc binding organises protein domains and determines the structure of protein complexes. Zinc fingers and related protein domains grip other molecules for protein–protein, protein–DNA/RNA, and protein–lipid interactions. And evidence is accumulating that many of these processes are controlled via regulated zinc(II) ion fluxes. Thus, not only is zinc tightly controlled but zinc(II) ion transients also control biological processes. At the cellular level, total zinc concentrations are as high as those of some major metabolites (≥0.25 mM). Zinc is compartmentalized in the cell, stored in organelles, released, and dynamically re-distributed by at least 24 zinc transporters and about a dozen metallothioneins. Mutations in these proteins are associated with many metabolic, infectious, and chronic diseases, with huge implications for a role of the zinc status in causing disease or influencing the progression of diseases. All of this biology is based on variations in zinc's coordination environments that modulate exchange kinetics from seconds to years, and determine whether or not zinc is a permanent cofactor or interacts only transiently with a protein. Remarkably, zinc complexes with sulphur donors from cysteines are redox active, thus linking redox-inert zinc and redox metabolism. The recent findings in zinc biology have huge impacts on the biosciences as zinc participates in virtually all cellular events. This themed issue of Metallomics was commissioned by the Royal Society of Chemistry (RSC) Editorial Team, in part as a result of their interactions with Zinc-UK (http://zinc-uk.org) and the International Society for Zinc Biology (http://iszb.org). Zinc-UK recently gained recognition through funding from COST (European Cooperation in Science and Technology) for the project Zinc-Net (http://zinc-net.com) that aims to bring together zincologists from Europe and other countries by providing funds for training early stage researchers in a gender-neutral scientific “zincscape”. The articles in this issue of Metallomics do not address all aspects of zinc biology nor is the coverage meant to be comprehensive. Rather, the articles give some flavour of latest developments and indicate the bright future of the field, which will be everything but the kitchen zinc.

Prof. Wolfgang Maret, King's College London, UK. Chair of the Metallomics Editorial Board.

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