Zinc Binding to MG53 Protein Facilitates Repair of Injury to Cell Membranes

J Biol Chem. 2015 May 29;290(22):13830-9. doi: 10.1074/jbc.M114.620690. Epub 2015 Apr 13.


Zinc is an essential trace element that participates in a wide range of biological functions, including wound healing. Although Zn(2+) deficiency has been linked to compromised wound healing and tissue repair in human diseases, the molecular mechanisms underlying Zn(2+)-mediated tissue repair remain unknown. Our previous studies established that MG53, a TRIM (tripartite motif) family protein, is an essential component of the cell membrane repair machinery. Domain homology analysis revealed that MG53 contains two Zn(2+)-binding motifs. Here, we show that Zn(2+) binding to MG53 is indispensable to assembly of the cell membrane repair machinery. Live cell imaging illustrated that Zn(2+) entry from extracellular space is essential for translocation of MG53-containing vesicles to the acute membrane injury sites for formation of a repair patch. The effect of Zn(2+) on membrane repair is abolished in mg53(-/-) muscle fibers, suggesting that MG53 functions as a potential target for Zn(2+) during membrane repair. Mutagenesis studies suggested that both RING and B-box motifs of MG53 constitute Zn(2+)-binding domains that contribute to MG53-mediated membrane repair. Overall, this study establishes a base for Zn(2+) interaction with MG53 in protection against injury to the cell membrane.

Keywords: E3 ubiquitin ligase; redox regulation; signaling; trafficking; vesicles.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Membrane / metabolism*
  • DNA Repair
  • Electrodes
  • Escherichia coli / metabolism
  • Humans
  • Membrane Proteins
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Muscle, Skeletal / metabolism
  • Mutation
  • Oxidation-Reduction
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Proteins / metabolism
  • Regenerative Medicine
  • Signal Transduction
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism
  • Wound Healing
  • Zinc / metabolism*


  • Carrier Proteins
  • MG53 protein, mouse
  • Membrane Proteins
  • Recombinant Proteins
  • TRIM72 protein, human
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases
  • Zinc