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Bacteriorhodopsin folds through a poorly organized transition state.

ABSTRACT: The folding mechanisms of helical membrane proteins remain largely uncharted. Here we characterize the kinetics of bacteriorhodopsin folding and employ ?-value analysis to explore the folding transition state. First, we developed and confirmed a kinetic model that allowed us to assess the rate of folding from SDS-denatured bacteriorhodopsin (bRU) and provides accurate thermodynamic information even under influence of retinal hydrolysis. Next, we obtained reliable ?-values for 16 mutants of bacteriorhodopsin with good coverage across the protein. Every ?-value was less than 0.4, indicating the transition state is not uniquely structured. We suggest that the transition state is a loosely organized ensemble of conformations.

SUBMITTER: Schlebach JP

PROVIDER: S-EPMC4277764 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Bacteriorhodopsin folds through a poorly organized transition state.

Schlebach Jonathan P JP Woodall Nicholas B NB Bowie James U JU Park Chiwook C

Journal of the American Chemical Society 20141117 47

The folding mechanisms of helical membrane proteins remain largely uncharted. Here we characterize the kinetics of bacteriorhodopsin folding and employ φ-value analysis to explore the folding transition state. First, we developed and confirmed a kinetic model that allowed us to assess the rate of folding from SDS-denatured bacteriorhodopsin (bRU) and provides accurate thermodynamic information even under influence of retinal hydrolysis. Next, we obtained reliable φ-values for 16 mutants of bacte ...[more]

PMID: 25369295

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