Predicting coupling limits from an experimentally determined energy landscape
作者： T. O. Street , C. M. Bradley , D. Barrick
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摘要: Repeat proteins are composed of tandem structural modules in which close contacts do not extend beyond adjacent repeats. Despite the local nature these contacts, repeat often unfold as a single, highly coupled unit. Previous studies on Notch ankyrin domain suggest that this lack equilibrium unfolding intermediates results both from stabilizing interfaces between each and roughly uniform distribution stability across folding energy landscape. To investigate idea, we have generated 15 variants with single multiple destabilizing substitutions make landscape uneven. By applying free additivity analysis to variants, quantified destabilization threshold over repeats 6 7 decouple 1–5. The coupling limit suggested by (≈4 kcal/mol) is also reflected m-value differences among transitions monitored CD versus fluorescence for all variants. All observations quantitatively predicted analyzing response experimentally determined increasing unevenness. These highlight importance achieving cooperative unfolding.
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