Bivalent Copper Ions Promote Fibrillar Aggregation of KCTD1 and Induce Cytotoxicity

Sci Rep. 2016 Sep 6:6:32658. doi: 10.1038/srep32658.

Abstract

Potassium channel tetramerization domain containing 1 (KCTD1) family members have a BTB/POZ domain, which can facilitate protein-protein interactions involved in the regulation of different signaling pathways. KCTD proteins have potential Zn(2+)/Cu(2+) binding sites with currently unknown structural and functional roles. We investigated potential Cu(2+)-specific effects on KCTD1 using circular dichroism, turbidity measurement, fluorescent dye binding, proteinase K (PK) digestion, cell proliferation and apoptosis assays. These experiments indicate that the KCTD1 secondary structure assumes greater β-sheet content and the proteins aggregate into a PK-resistant form under 20 μM Cu(2+), and this β-sheet-rich aggregation with Cu(2+) promotes fibril formation, which results in increased cell toxicity by apoptosis. Our results reveal a novel role for Cu(2+) in determining the structure and function of KCTD1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line
  • Cell Survival
  • Circular Dichroism
  • Co-Repressor Proteins
  • Copper / metabolism*
  • Humans
  • Microscopy, Electron, Transmission
  • Protein Structure, Secondary
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*
  • Spectrometry, Fluorescence

Substances

  • Co-Repressor Proteins
  • KCTD1 protein, human
  • Repressor Proteins
  • Copper