Many proteins – including the heat-shock protein Hsp90 – can adopt several distinct conformations. Herein, single molecule FRET was used to detect the time evolution of Hsp90’s conformational state. To obtain a quantitative description thereof, a single molecule analysis of complex kinetic sequences (SMACKS) was developed. Based on various experiments in and out of equilibrium, SMACKS provided unparalleled insights in the dynamic structure-function relationship in Hsp90. Although the global conformational changes occur independently of ATP hydrolysis, the ATPase activity itself is substantially affected by the manipulation of Hsp90’s conformational energy landscape.
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Many proteins – including the heat-shock protein Hsp90 – can adopt several distinct conformations. Herein, single molecule FRET was used to detect the time evolution of Hsp90’s conformational state. To obtain a quantitative description thereof, a single molecule analysis of complex kinetic sequences (SMACKS) was developed. Based on various experiments in and out of equilibrium, SMACKS provided unparalleled insights in the dynamic structure-function relationship in Hsp90. Although the global conf...
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