JBC Thematic Series on
Metals in Biology
This spring, the Journal of Biological Chemistry unveiled a thematic minireview series, “Metals in Biology 2012,” the fourth installment of an ongoing series coordinated by JBC Associate Editor F. Peter Guengerich featuring the significant role of metals in biochemistry and human health. The first, “Metals in Biology,” discussed iron, copper and selenium. The second, “Metals in Biology II,” included reviews of iron, zinc, nickel, vanadium and arsenic; while the third, “Metals in Biology III: Iron Management by Eukaryotic Cells,” illuminated iron homeostasis. The newest installment concentrates on metal transport and homeostasis. Understanding these elements of metal biology is important, given that metals are crucial to many biochemical reactions yet potentially detrimental when present in excess or misregulated.
To start, José M. Argüello and colleagues discuss the transport of transition metals across membranes for their delivery throughout the cell in “Metal transport across biomembranes: emerging models for a distinct chemistry.” The authors review specific features of transition metal transporters, including protein-protein interactions at the site of metal transfer, metal coordination configurations and slow transport rates. To illustrate these aspects, they focus on recent structural and biochemical findings of four transporter families — P1B-ATPases, resistance-nodulation-cell division transporters, copper uptake transporters and cation diffusion facilitator transporters.
Caroline C. Philpott assesses recent findings in the field of iron chaperones in “Coming into view: eukaryotic iron chaperones and intracellular iron delivery.” The review focuses on three types of eukaryotic iron chaperones and discusses the roles of each: 1) frataxin, which participates in the mitochondrial formation of iron-sulfur clusters; 2) poly(rC)-binding proteins, which deliver iron to ferritin and other iron-dependent proteins; and 3) Grx3-type monothiol glutaredoxins, which play a role in iron sensing in budding yeast and also affect iron-sulfur cluster formation. As a summary, the review presents a model to describe putative mechanisms for iron delivery in mammalian cells.
Next, Colin Correnti and Roland K. Strong cover the roles of siderophores — small, secreted compounds with a high affinity for ferric iron — and siderophore-binding proteins during bacterial infection of mammalian hosts in “Mammalian siderophores, siderophore-binding lipocalins and the labile iron pool.” While much is known about these players and processes, the presence and roles of endogenous mammalian siderophores have been elusive. The authors discuss recent findings that provide evidence of mammalian siderophores and their roles in iron transport in the urinary tract and during tumorigenesis.
Yvain Nicolet and Juan C. Fontecilla-Camps focus on the proteins responsible for active-site maturation of the metalloenzyme [FeFe]-hydrogenase in “Structure-function relationships in [FeFe]-hydrogenase active site maturation.” The authors present structural and biochemical data for three maturase proteins, HydF, HydG and HydE, reviewing their known (HydF, HydG) and probable (HydE) roles. Additionally, the article evaluates various proposals for the bridgehead atom of the dithiolate ligand within the [FeFe]-hydrogenase active site and discusses the perplexity of active [FeFe]-hydrogenase production upon expression of the structural gene in organisms lacking the maturase proteins.
J. Dafhne Aguirre and Valeria C. Culotta discuss the protective effects of manganese and the antagonistic role of iron during oxidative stress in “Battles with iron: manganese in oxidative stress protection.” The review describes two ways in which manganese can protect cells from oxidative stress: as a cofactor of manganese/iron-superoxide dismutases and as nonproteinaceous manganese complexes. The authors examine mitochondrial mechanisms that ensure manganese as the cofactor for manganese-superoxide dismutase 2 despite the low levels of manganese compared to iron in mitochondria and review the composition and cellular regulation of antioxidant manganese complexes. Additionally, the review touches briefly upon the role of manganese during bacterial infection.
In the final review, “Copper homeostasis at the host-pathogen interface,” Victoria Hodgkinson and Michael J. Petris cover three processes by which bacteria resist high copper levels as a result of host defense – removal of copper out of the cytoplasm, capture of copper via copper binding proteins and reduction of copper toxicity by oxidation of Cu(I) to Cu(II). The authors also discuss the regulation of copper as a factor in the virulence of two highly analyzed pathogens, Mycobacterium tuberculosis and Salmonella typhimurium, and the management of host copper during infection.
These six reviews reveal the complexity of metalloproteins and metal transport and the importance of proper metal regulation during oxidative stress and pathogen infection. While they illuminate the processes of metal transport and homeostasis in eukaryotic cells and bacteria, there are still many unknowns. As suggested by Guengerich in the introduction to this installment, important areas of metal biology remain as future topics for this thematic series, and plans are under way for the next series.
Danielle Gutierrez (email@example.com) is a freelance science writer based in Corpus Christi, Texas.