Bivalent Copper Ions Promote Fibrillar Aggregation of KCTD1 and Induce Cytotoxicity.
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.
School of Basic Medical Sciences, Wuhan University, Wuhan 430072, P.R. China.
Zhepeng
Z
Liu
School of Basic Medical Sciences, Wuhan University, Wuhan 430072, P.R. China.
Feifei
F
Song
School of Basic Medical Sciences, Wuhan University, Wuhan 430072, P.R. China.
Zhi-Li
ZL
Ma
School of Basic Medical Sciences, Wuhan University, Wuhan 430072, P.R. China.
Qiushuang
Q
Xiong
School of Basic Medical Sciences, Wuhan University, Wuhan 430072, P.R. China.
Jingwen
J
Wang
School of Basic Medical Sciences, Wuhan University, Wuhan 430072, P.R. China.
Deyin
D
Guo
School of Basic Medical Sciences, Wuhan University, Wuhan 430072, P.R. China.
Guihong
G
Sun
D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival; D002942:Circular Dichroism; D056970:Co-Repressor Proteins; D003300:Copper / Q000378:metabolism*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D017433:Protein Structure, Secondary; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D056970:Co-Repressor Proteins; C529677:KCTD1 protein, human; D012097:Repressor Proteins; D003300:Copper