Quantifying the Oligomeric State of hZIP4 on the Surface of Cells

Biochemistry. 2019 Apr 2;58(13):1705-1708. doi: 10.1021/acs.biochem.9b00131. Epub 2019 Mar 20.


The human (h) zinc transporter ZIP4 is expressed on the plasma membrane and functions to increase cytosolic zinc levels. Mutations in hZIP4 cause the disease acrodermatitis enteropathica. Dysfunction in the regulation of hZIP4 has also been indicated in solid tissue cancers, including pancreatic and prostate cancer. Although structural studies of the extracellular domain and computational modeling of the membrane domain suggest hZIP4 exists as a dimer, the oligomerization status of hZIP4 in the plasma membrane of mammalian cells has not been directly quantified in vivo. Here, the oligomeric state of hZIP4 expressed in HEK293 cells was quantified using fluorescence correlation spectroscopy. hZIP4 was tagged with eGFP, and by comparing brightness values (ε) of monomer and tandem eGFP constructs to that of an hZIP4/eGFP, we show that hZIP4 is a dimer. Determining that hZIP4 is a dimer is an important step toward understanding the function and processing of the protein, which can provide more insight into how diseases affected by hZIP4 occur and can be managed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cation Transport Proteins / chemistry*
  • Cell Membrane / chemistry
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • Protein Domains
  • Protein Multimerization
  • Spectrometry, Fluorescence


  • Cation Transport Proteins
  • SLC39A4 protein, human