Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoprotein.
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Toogood HS, van Thiel A, Scrutton NS, Leys D
Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoprotein.
J Biol Chem. 2005 Aug 26;280(34):30361-6. Epub 2005 Jun 23.
- PubMed ID
- 15975918 [ View in PubMed]
- Abstract
Crystal structures of protein complexes with electron-transferring flavoprotein (ETF) have revealed a dual protein-protein interface with one region serving as anchor while the ETF FAD domain samples available space within the complex. We show that mutation of the conserved Glu-165beta in human ETF leads to drastically modulated rates of interprotein electron transfer with both medium chain acyl-CoA dehydrogenase and dimethylglycine dehydrogenase. The crystal structure of free E165betaA ETF is essentially identical to that of wild-type ETF, but the crystal structure of the E165betaA ETF.medium chain acyl-CoA dehydrogenase complex reveals clear electron density for the FAD domain in a position optimal for fast interprotein electron transfer. Based on our observations, we present a dynamic multistate model for conformational sampling that for the wild-type ETF. medium chain acyl-CoA dehydrogenase complex involves random motion between three distinct positions for the ETF FAD domain. ETF Glu-165beta plays a key role in stabilizing positions incompatible with fast interprotein electron transfer, thus ensuring high rates of complex dissociation.