Proteins metal transport

Meanwhile chromodulin, stored in apo form in the cell cytosol and nucleus, is metallated by transfer of Cr(III) from the blood to insulin-dependent cells, perhaps by the metal transport protein transferrin. 

A biological example of E° is the reduction of Fe(III) in the protein transferrin, which was introduced in Figure 7-4. This protein has two Fe(III)-binding sites, one in each half of the molecule designated C and N for the carboxyl and amino terminals of the peptide chain. Transferrin carries Fe(III) through the blood to cells that require iron. Membranes of these cells have a receptor that binds Fe(III)-transferrin and takes it into a compartment called an endosome into which H is pumped to lower the pH to —5.8. Iron is released from transferrin in the endosome and continues into the cell as Fe(II) attached to an intracellular metal-transport protein. The entire cycle of transferrin uptake, metal removal, and transferrin release back to the bloodstream takes 1-2 min. The time required for Fe(III) to dissociate from transferrin at pH 5.8 is —6 min, which is too long to account for release in the endosome. The reduction potential of Fe(IH)-transferrin at pH 5.8 is E° = —0.52 V, which is too low for physiologic reductants to reach. 

Zinc efflux is mediated by a zinc exporter known as ZntA (Zn + transport or tolerance), a membrane protein which was identified through studies of bacterial strains that were hypersensitive to zinc and cadmium. Sequence inspection revealed that ZntA was a member of the family of cation transport P-type ATPases, a major family of ion-translocating membrane proteins in which ATPase activity in one portion of the protein is used to phophorylate an aspartate within a highly conserved amino acid sequence, DKTG, in another portion of the protein. The cysteine rich N-terminus of these soft metal transport proteins contains several metal-binding sites. How the chemical energy released by ATP hydrolysis results in metal ion transport is not yet known, in part because there is only partial information about the structures of these proteins. The bacterial zinc exporter also pumps cadmium and lead and is therefore also involved in protection from heavy metal toxicity (see Metal Ion Toxicity). 

In order for a metal ion to reach its intracellular protein target, a number of complex barriers must be crossed. First, the metal existing in the extracellular environment must traverse the plasma membrane of the cell. The lipid bilayers of cellular membranes are generally impermeable to metals and cellular uptake of the ion requires the action of metal transport proteins. A host of membrane transporters reside at the cell surface, some of which are specific for certain ions (e.g. only copper or only zinc), while others are more promiscuous in their choice of metal ion substrate (e.g. can transport both copper and zinc). But all are designed to ensure that cells acquire proper levels of the essential heavy metal ions such as copper, zinc, iron, and manganese. 

Peptides and proteins could be efficient metal binding ligands, because they have the functional groups for metal binding in their amino acid residues, and they can be produced at low cost by recombinant technologies. While many peptides and proteins are known to work as metal transport proteins in biological systems, metallothioneins (cysteine rich proteins with molecular weight of ca. 7 kDa) have attracted researchers attention for decades because they bind heavy metals in vivo [2]. The metallothioneins are considered to be involved in detoxication and metabolism of heavy metals. 

Enterocytes in the proximal duodenum are responsible for absorption of iron. Incoming iron in the Fe " state is reduced to Fe " by a ferrireductase present on the surface of enterocytes. Vitamin C in food also favors reduction of ferric iron to ferrous iron. The transfer of iron from the apical surfaces of enterocytes into their interiors is performed by a proton-coupled divalent metal transporter (DMTl). This protein is not specific for iron, as it can transport a wide variety of divalent cations. 

These results may be viewed in the wider context of interactions between potential ligands of multifunctional xenobiotics and metal cations in aquatic environments and the subtle effects of the oxidation level of cations such as Fe. The Fe status of a bacterial culture has an important influence on synthesis of the redox systems of the cell since many of the electron transport proteins contain Fe. This is not generally evaluated systematically, although the degradation of tetrachloromethane by a strain of Pseudomonas sp. under denitrifying conditions clearly illustrated the adverse effect of Fe on the biotransformation of the substrate (Lewis and Crawford 1993 Tatara et al. 1993). This possibility should therefore be taken into account in the application of such organisms to bioremediation programs. 

Mucosal cells can take up iron from the lumen across their brush border membranes by at least two separate pathways, both of which are thought to be receptor mediated. Non-haem dietary iron seems most likely to be taken across the brush border membrane after reduction by an apical, membrane-bound, ferrireductase and subsequent transport of the Fe2+ by a divalent metal-ion transporter protein, known both as DCT1 and Nramp2. 

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