The mechanism of temperature-induced bacterial HtrA activation |
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Authors: | Kim Dong Young Kwon Eunju Shin Yeon-Kyun Kweon Dae-Hyuk Kim Kyeong Kyu |
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Affiliation: | 1 Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea 2 Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, IA 50011, USA 3 Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Korea |
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Abstract: | High-temperature requirement A (HtrA) protein has been known as a moonlighting protein that plays dual roles as a molecular chaperone and as a protease. The proteolytic activity of HtrA is switched on at elevated temperatures, whereas the chaperone function predominates at normal temperatures. The temperature-regulated functional switch of HtrA appears to be critical for the control of the stability of cellular proteins, as well as for the elimination of denatured proteins in order to maintain viability. Although certain conformational changes are expected to be concurrent with the functional activation of HtrA proteolysis, the molecular mechanisms inherent to this process have yet to be elucidated. Spin labeling electron paramagnetic resonance and fluorescence spectroscopy experiments on the HtrA from Thermotoga maritima (Tm HtrA) have shown that a helical lid (HL) that covers the active site is lifted up to expose the catalytic and substrate-binding sites to the solvent at elevated temperatures, whereas the overall structure is maintained over a wide temperature range. Results indicate that the proteolytic activity of Tm HtrA is turned on by the geometric change occurring around the HL, resulting in a substrate-accessible path. In conclusion, the functional switch of Tm HtrA is embedded in the sentinel of the HL in terms of substrate accessibility. |
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Keywords: | EPR, electron paramagnetic resonance SDSL, site-directed spin labeling HtrA, high-temperature requirement A Tm, Thermotoga maritima HL, a short lid-like α-helix |
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