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Article Dans Une Revue Biophysical Journal Année : 2015

A Well-Balanced Preexisting Equilibrium Governs Electron Flux Efficiency of a Multidomain Diflavin Reductase

Résumé

Diflavin reductases are bidomain electron transfer proteins in which structural reorientation is necessary to account for the various intramolecular and intermolecular electron transfer steps. Using small-angle x-ray scattering and nuclear magnetic resonance data, we describe the conformational free-energy landscape of the NADPH-cytochrome P450 reductase (CPR), a typical bidomain redox enzyme composed of two covalently-bound flavin domains, under various experimental conditions. The CPR enzyme exists in a salt- and pH-dependent rapid equilibrium between a previously described rigid, locked state and a newly characterized, highly flexible, unlocked state. We further establish that maximal electron flux through CPR is conditioned by adjustable stability of the locked-state domain interface under resting conditions. This is rationalized by a kinetic scheme coupling rapid conformational sampling and slow chemical reaction rates. Regulated domain interface stability associated with fast stochastic domain contacts during the catalytic cycle thus provides, to our knowledge, a new paradigm for improving our understanding of multidomain enzyme function.

Dates et versions

hal-01142871 , version 1 (16-04-2015)

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Oriane Frances, Fataneh Fatemi, Denis Pompon, Eric Guittet, Christina Sizun, et al.. A Well-Balanced Preexisting Equilibrium Governs Electron Flux Efficiency of a Multidomain Diflavin Reductase. Biophysical Journal, 2015, 108 (6), pp.1527-1536. ⟨10.1016/j.bpj.2015.01.032⟩. ⟨hal-01142871⟩
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