Protein folding and unfolding in microseconds to nanoseconds by experiment and simulation.
The Engrailed Homeodomain protein has the highest refolding and unfolding rate constants directly observed to date. Temperature jump relaxation measurements gave a refolding rate constant of 37,500 s(-1) in water at 25 degrees C, rising to 51,000 s(-1) around 42 degrees C. The unfolding rate constant was 1,100 s(-1) in water at 25 degrees C and 205,000 s(-1) at 63 degrees C. The unfolding half-life is extrapolated to be approximately 7.5 ns at 100 degrees C, which allows real-time molecular dynamics unfolding simulations to be tested on this system at a realistic temperature. Preliminary simulations did indeed conform to unfolding on this time scale. Further, similar transition states were observed in simulations at 100 degrees C and 225 degrees C, suggesting that high-temperature simulations provide results applicable to lower temperatures.
Mayor
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Medical Research Council Centre for Protein Engineering and Cambridge University Chemical Laboratory, Hills Road, Cambridge CB2 2QH, United Kingdom.
Johnson
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Daggett
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Fersht
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D018398:Homeodomain Proteins / Q000737:chemistry*; D007700:Kinetics; D017510:Protein Folding; D014157:Transcription Factors
D018398:Homeodomain Proteins; D014157:Transcription Factors; C106185:engrailed homeobox proteins