Title of article :
Selective Cu2+ Binding, Redox Silencing, and Cytoprotective Effects of the Small Heat Shock Proteins αA- and αB-Crystallin
Author/Authors :
Md. Faiz Ahmad، نويسنده , , Devendra Singh، نويسنده , , Aftab Taiyab، نويسنده , , Tangirala Ramakrishna، نويسنده , , Bakthisaran Raman، نويسنده , , Ch. Mohan Rao، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2008
Abstract :
Oxidative stress and Cu2+ have been implicated in several neurodegenerative diseases and in cataract. Oxidative stress, as well as Cu2+, is also known to induce the expression of the small heat shock proteins α-crystallins. However, the role of α-crystallins in oxidative stress and in Cu2+-mediated processes is not clearly understood. We demonstrate using fluorescence and isothermal titration calorimetry that α-crystallins (αA- and αB-crystallin and its phosphorylation mimic, 3DαB-crystallin) bind Cu2+ with close to picomolar range affinity. The presence of other tested divalent cations such as Zn2+, Mg2+, and Ca2+ does not affect Cu2+ binding, indicating selectivity of the Cu2+-binding site(s) in α-crystallins. Cu2+ binding induces structural changes and increase in the hydrodynamic radii of α-crystallins. Cu2+ binding increases the stability of α-crystallins towards guanidinium chloride-induced unfolding. Chaperone activity of αA-crystallin increases significantly upon Cu2+ binding. α-Crystallins rescue amyloid beta peptide, Aβ1–40, from Cu2+-induced aggregation in vitro. α-Crystallins inhibit Cu2+-induced oxidation of ascorbate and, hence, prevent the generation of reactive oxygen species. Interestingly, α-synuclein, a Cu2+-binding protein, does not inhibit this oxidation process significantly. We find that the Cu2+-sequestering (or redox-silencing) property of α-crystallins confers cytoprotection. To the best of our knowledge, this is the first study to reveal high affinity (close to picomolar) for Cu2+ binding and redox silencing of Cu2+ by any heat shock protein. Thus, our study ascribes a novel functional role to α-crystallins in Cu2+ homeostasis and helps in understanding their protective role in neurodegenerative diseases and cataract.
Keywords :
chaperone , ?-crystallins , Cu2+ binding , redox silencing , cytoprotection
Journal title :
Journal of Molecular Biology
Journal title :
Journal of Molecular Biology