Dynamics driving function - New insights from electron transferring flavoproteins and partner complexes

Helen S. Toogood, David Leys, Nigel S. Scrutton

    Research output: Contribution to journalArticlepeer-review


    Electron transferring flavoproteins (ETFs) are soluble heterodimeric FAD-containing proteins that function primarily as soluble electron carriers between various flavoprotein dehydrogenases. ETF is positioned at a key metabolic branch point, responsible for transferring electrons from up to 10 primary dehydrogenases to the membrane-bound respiratory chain. Clinical mutations of ETF result in the often fatal disease glutaric aciduria type II. Structural and biophysical studies of ETF in complex with partner proteins have shown that ETF partitions the functions of partner binding and electron transfer between (a) a 'recognition loop', which acts as a static anchor at the ETF-partner interface, and (b) a highly mobile redox-active FAD domain. Together, this enables the FAD domain of ETF to sample a range of conformations, some compatible with fast interprotein electron transfer. This 'conformational sampling' enables ETF to recognize structurally distinct partners, whilst also maintaining a degree of specificity. Complex formation triggers mobility of the FAD domain, an 'induced disorder' mechanism contrasting with the more generally accepted models of protein-protein interaction by induced fit mechanisms. We discuss the implications of the highly dynamic nature of ETFs in biological interprotein electron transfer. ETF complexes point to mechanisms of electron transfer in which 'dynamics drive function', a feature that is probably widespread in biology given the modular assembly and flexible nature of biological electron transfer systems. © 2007 The Authors.
    Original languageEnglish
    Pages (from-to)5481-5504
    Number of pages23
    JournalFEBS Journal
    Issue number21
    Publication statusPublished - Nov 2007


    • Acyl-CoA dehydrogenase
    • Conformational sampling
    • Electron transferring flavoprotein
    • Imprinting
    • Trimethylamine dehydrogenase


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