| | Gentamicin inhibits HSP70-assisted protein folding by interfering with substrate recognitionEdited by Miguel De la Rosa Received 29 September 2009; received in revised form 24 November 2009; accepted 10 December 2009. published online 22 December 2009. Abstract We previously reported that gentamicin (GM) specifically binds to heat-shock protein with subunit molecular masses of 70 kDa (HSP70). In the present study, we have investigated the effects of GM binding on HSP70-assisted protein folding in vitro. The C-terminal, and not the N-terminal of HSP70 was found to bind to GM. GM significantly suppressed refolding of firefly luciferase in the presence of HSP70 and HSP40, although the ATPase activity of HSP70 was unaffected by GM. A surface plasmon resonance analysis revealed that GM specifically interferes with the binding of HSP70 to a model peptide that mimics the exposed hydrophobic surface of the folding intermediates. These results indicated that GM inhibits the chaperone activity of HSP70 and may suppress protein folding via inhibition of HSP70 in vivo. a Department of Life Science, Faculty of Engineering and Resource Science, Akita University, 1-1 Tegata Gakuen Town, Akita City 010-8502, Japan b Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, Japan c Third Department of Internal Medicine, Akita University School of Medicine, Akita 010-8543, Japan  Corresponding author. Fax: +81 18 883 3041.
PII: S0014-5793(09)01067-9 doi:10.1016/j.febslet.2009.12.021 © 2009 Federation of European Biochemical Societies. Published by Elsevier BV. All rights reserved. | |
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ABSTRACT
