Poster Presentation 2014 International Biophysics Congress

Metal-dependent interactions of metallothionein-3 with amyloid-β peptide and possible physiological implications (#643)

Zhongxiu Jiang 1 , Juan Xiang 1
  1. Central South University, Yuelu, Changsha, China

Alzheimer's disease (AD) is a progressive and devastating neurodegenerative pathology that affects several tens of millions of victims worldwide. Aberrant interactions of metal ions with amyloid-β peptide(Aβ) can potentiate AD by participating in the aggregation process of Aβ and in the generation of reactive oxygen species (ROS). Metallothionein-3 (MT3) is believed to play an important role in the progression of AD due to its ability on maintaining metal homeostasis and its aberrant expression in AD brains. However, the related molecular mechanism is not clear. In this work, the metal-dependent interactions of MT3 with Aβ were studied. SPR results show that Zn-MT3 has a stronger affinity to Aβ (Kd: ∼2μM) than Cu-MT3 (Kd: ∼47μM). MD results show that both Pro7 and Pro9 in Zn-MT3 face outwards with their five-member rings in parallel, favoring their binding with aromatic residues via CH/π interactions. Two aromatic residues (Tyr10 and Phe4) in Aβ are identified as the specific binding sites for MT3. MS results confirm the formation of Zn-MT3/Aβ complex. Due to the high concentration of MT3 in vivo (∼30 μM), its effect on protecting neurons can be deduced. In which, Zn-MT3/Aβ complex forms under physiological conditions, inhibiting the neurotoxicity of Aβ/Cu2+ by effectively capture free Cu2+. Moreover, the dissociation of Cu-MT from Aβ favors the degradation of Cu2+.