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Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoprotein.

Toogood HS, van Thiel A, Scrutton NS, Leys D
J Biol Chem 280 30361-6 (2005)
Cited: 26 times
EuropePMC logo PMID: 15975918

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.

Reviews - 2a1t mentioned but not cited (1)

  1. Electron transfer flavoprotein and its role in mitochondrial energy metabolism in health and disease. Henriques BJ, Katrine Jentoft Olsen R, Gomes CM, Bross P. Gene 776 145407 (2021)

Articles - 2a1t mentioned but not cited (7)

  1. Sirtuin 3 (SIRT3) protein regulates long-chain acyl-CoA dehydrogenase by deacetylating conserved lysines near the active site. Bharathi SS, Zhang Y, Mohsen AW, Uppala R, Balasubramani M, Schreiber E, Uechi G, Beck ME, Rardin MJ, Vockley J, Verdin E, Gibson BW, Hirschey MD, Goetzman ES. J Biol Chem 288 33837-33847 (2013)
  2. Studies on the mechanism of electron bifurcation catalyzed by electron transferring flavoprotein (Etf) and butyryl-CoA dehydrogenase (Bcd) of Acidaminococcus fermentans. Chowdhury NP, Mowafy AM, Demmer JK, Upadhyay V, Koelzer S, Jayamani E, Kahnt J, Hornung M, Demmer U, Ermler U, Buckel W. J Biol Chem 289 5145-5157 (2014)
  3. Electron transfer flavoprotein domain II orientation monitored using double electron-electron resonance between an enzymatically reduced, native FAD cofactor, and spin labels. Swanson MA, Kathirvelu V, Majtan T, Frerman FE, Eaton GR, Eaton SS. Protein Sci 20 610-620 (2011)
  4. DEER distance measurement between a spin label and a native FAD semiquinone in electron transfer flavoprotein. Swanson MA, Kathirvelu V, Majtan T, Frerman FE, Eaton GR, Eaton SS. J Am Chem Soc 131 15978-15979 (2009)
  5. Oxidation of the FAD cofactor to the 8-formyl-derivative in human electron-transferring flavoprotein. Augustin P, Toplak M, Fuchs K, Gerstmann EC, Prassl R, Winkler A, Macheroux P. J Biol Chem 293 2829-2840 (2018)
  6. Kinetic and spectral properties of isovaleryl-CoA dehydrogenase and interaction with ligands. Mohsen AW, Vockley J. Biochimie 108 108-119 (2015)
  7. Molecular mechanism of interactions between ACAD9 and binding partners in mitochondrial respiratory complex I assembly. Xia C, Lou B, Fu Z, Mohsen AW, Shen AL, Vockley J, Kim JP. iScience 24 103153 (2021)


Reviews citing this publication (1)

  1. Dynamics driving function: new insights from electron transferring flavoproteins and partner complexes. Toogood HS, Leys D, Scrutton NS. FEBS J 274 5481-5504 (2007)

Articles citing this publication (17)

  1. Regulation of FMN subdomain interactions and function in neuronal nitric oxide synthase. Ilagan RP, Tejero J, Aulak KS, Ray SS, Hemann C, Wang ZQ, Gangoda M, Zweier JL, Stuehr DJ. Biochemistry 48 3864-3876 (2009)
  2. Surface charges and regulation of FMN to heme electron transfer in nitric-oxide synthase. Tejero J, Hannibal L, Mustovich A, Stuehr DJ. J Biol Chem 285 27232-27240 (2010)
  3. Compared effects of missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase deficiency: Combined analysis by structural, functional and pharmacological approaches. Gobin-Limballe S, McAndrew RP, Djouadi F, Kim JJ, Bastin J. Biochim Biophys Acta 1802 478-484 (2010)
  4. Structure and function of seed storage proteins in faba bean (Vicia faba L.). Liu Y, Wu X, Hou W, Li P, Sha W, Tian Y. 3 Biotech 7 74 (2017)
  5. Cryoelectron microscopy structure and mechanism of the membrane-associated electron-bifurcating flavoprotein Fix/EtfABCX. Feng X, Schut GJ, Lipscomb GL, Li H, Adams MWW, Adams MWW. Proc Natl Acad Sci U S A 118 e2016978118 (2021)
  6. Structural and Functional Characterization of an Electron Transfer Flavoprotein Involved in Toluene Degradation in Strictly Anaerobic Bacteria. Vogt MS, Schühle K, Kölzer S, Peschke P, Chowdhury NP, Kleinsorge D, Buckel W, Essen LO, Heider J. J Bacteriol 201 e00326-19 (2019)
  7. A polymorphic position in electron transfer flavoprotein modulates kinetic stability as evidenced by thermal stress. Henriques BJ, Fisher MT, Bross P, Gomes CM. FEBS Lett 585 505-510 (2011)
  8. Electronic coupling through natural amino acids. Berstis L, Beckham GT, Crowley MF. J Chem Phys 143 225102 (2015)
  9. The purified recombinant precursor of rat mitochondrial dimethylglycine dehydrogenase binds FAD via an autocatalytic reaction. Brizio C, Brandsch R, Douka M, Wait R, Barile M. Int J Biol Macromol 42 455-462 (2008)
  10. Molecular Basis for Converting (2S)-Methylsuccinyl-CoA Dehydrogenase into an Oxidase. Burgener S, Schwander T, Romero E, Fraaije MW, Erb TJ. Molecules 23 E68 (2017)
  11. Contrasting roles for two conserved arginines: Stabilizing flavin semiquinone or quaternary structure, in bifurcating electron transfer flavoproteins. Mohamed-Raseek N, Miller AF. J Biol Chem 298 101733 (2022)
  12. Spectroscopic evidence for direct flavin-flavin contact in a bifurcating electron transfer flavoprotein. Duan HD, Mohamed-Raseek N, Miller AF. J Biol Chem 295 12618-12634 (2020)
  13. A conformational sampling model for radical catalysis in pyridoxal phosphate- and cobalamin-dependent enzymes. Menon BR, Fisher K, Rigby SE, Scrutton NS, Leys D. J Biol Chem 289 34161-34174 (2014)
  14. Closing the gap: yeast electron-transferring flavoprotein links the oxidation of d-lactate and d-α-hydroxyglutarate to energy production via the respiratory chain. Toplak M, Brunner J, Tabib CR, Macheroux P. FEBS J 286 3611-3628 (2019)
  15. Isomers in the excited state of electron-transferring flavoprotein from Megasphaera elsdenii: spectral resolution from the time-resolved fluorescence spectra. Sato K, Nishina Y, Shiga K, Tanaka F. J Photochem Photobiol B 90 134-140 (2008)
  16. Noncovalent interactions that tune the reactivities of the flavins in bifurcating electron transferring flavoprotein. González-Viegas M, Kar RK, Miller AF, Mroginski MA. J Biol Chem 299 104762 (2023)
  17. Unusual reactivity of a flavin in a bifurcating electron-transferring flavoprotein leads to flavin modification and a charge-transfer complex. Mohamed-Raseek N, van Galen C, Stanley R, Miller AF. J Biol Chem 298 102606 (2022)


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