TY - JOUR
T1 - Are zinc-finger domains of protein kinase C dynamic structures that unfold by lipid or redox activation?
AU - Zhao, Feng
AU - Ilbert, Marianne
AU - Varadan, Ranjani
AU - Cremers, Claudia M.
AU - Hoyos, Beatrice
AU - Acin-Perez, Rebeca
AU - Vinogradov, Valerie
AU - Cowburn, David
AU - Jakob, Ursula
AU - Hammerling, Ulrich
PY - 2011/3/1
Y1 - 2011/3/1
N2 - Protein kinase C (PKC) is activated by lipid second messengers or redox action, raising the question whether these activation modes involve the same or alternate mechanisms. Here we show that both lipid activators and oxidation target the zinc-finger domains of PKC, suggesting a unifying activation mechanism. We found that lipid agonist-binding or redox action leads to zinc release and disassembly of zinc fingers, thus triggering large-scale unfolding that underlies conversion to the active enzyme. These results suggest that PKC zinc fingers, originally considered purely structural devices, are in fact redox-sensitive flexible hinges, whose conformation is controlled both by redox conditions and lipid agonists.
AB - Protein kinase C (PKC) is activated by lipid second messengers or redox action, raising the question whether these activation modes involve the same or alternate mechanisms. Here we show that both lipid activators and oxidation target the zinc-finger domains of PKC, suggesting a unifying activation mechanism. We found that lipid agonist-binding or redox action leads to zinc release and disassembly of zinc fingers, thus triggering large-scale unfolding that underlies conversion to the active enzyme. These results suggest that PKC zinc fingers, originally considered purely structural devices, are in fact redox-sensitive flexible hinges, whose conformation is controlled both by redox conditions and lipid agonists.
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U2 - 10.1089/ars.2010.3773
DO - 10.1089/ars.2010.3773
M3 - Article
C2 - 21067413
AN - SCOPUS:79551674547
SN - 1523-0864
VL - 14
SP - 757
EP - 766
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 5
ER -