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The human ZIP4 transporter has two distinct binding affinities and mediates transport of multiple transition metals.
MedLine Citation:
PMID:  22242765     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Zinc is the second most abundant transition metal in the body. Despite the fact that hundreds of biomolecules require zinc for proper function and/or structure, the mechanism of zinc transport into cells is not well-understood. The ZIP (Zrt- and Irt-like proteins; SLC39A) family of proteins acts to increase cytosolic concentrations of zinc. Mutations in one member of the ZIP family of proteins, the human ZIP4 (hZIP4; SLC39A4) protein, can result in the disease acrodermatitis enteropathica (AE). AE is characterized by growth retardation and diarrhea, as well as behavioral and neurological disturbances. While the cellular distribution of hZIP4 protein expression has been elucidated, the cation specificity, kinetic parameters of zinc transport and residues involved in cation translocation are unresolved questions. Therefore, we have established a high signal to noise zinc uptake assay following heterologous expression of hZIP4 in Xenopus laevis oocytes. The results from our experiments have demonstrated that zinc, copper (II) and nickel can be transported by hZIP4 when the cation concentration is in the micromolar range. We have also identified a nanomolar binding affinity where copper (II) and zinc can be transported. In contrast, under these conditions, nickel can bind, but is not transported by hZIP4. Finally, labeling of hZIP4 with maleimide or DEPC indicates that extracellularly accessible histidine, but not cysteine, residues are required, either directly or indirectly, for cation uptake. The results from our experiments describe at least two coordination sites for divalent cations and provide a new framework to investigate the ZIP family of proteins.
Authors:
Sagar Antala; Robert E Dempski
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-11
Journal Detail:
Title:  Biochemistry     Volume:  -     ISSN:  1520-4995     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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