Protein Dynamics Enhance Electronic Coupling in Electron Transfer Complexes

Chohan, Kamaldeep K.; Jones, Matthew; Grossmann, J. Günter; Frerman, Frank E.; Scrutton, Nigel S.; Sutcliffe, Michael J.

doi:10.1074/jbc.m101341200

Cited by 39 publications

(60 citation statements)

References 37 publications

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“…The sample-to-detector distance of 1.5 m and protein concentrations of approximately 15 mg/ml were chosen to reveal the scattering behavior in the scattering range 0.01 Å Ϫ1 Յ s Յ 0.08 Å Ϫ1 (s is the modulus of the momentum transfer and defined as s ϭ 2 sin ⌰/, where 2⌰ is the scattering angle and ϭ 1.54 Å is the x-ray wavelength). As established by our previous studies (26,27), this scattering interval is ideal in directly highlighting any differences in the scattering characteristics of the two protein states as a result of possible domain reorganizations. Further information with regards to data collection, reduction, and analysis have been described previously in detail (26,27).…”

Section: Methodsmentioning

confidence: 99%

“…As established by our previous studies (26,27), this scattering interval is ideal in directly highlighting any differences in the scattering characteristics of the two protein states as a result of possible domain reorganizations. Further information with regards to data collection, reduction, and analysis have been described previously in detail (26,27).…”

Section: Methodsmentioning

confidence: 99%

“…Also, large-scale conformational change has been suggested, from x-ray studies, as a prerequisite for efficient electron transfer; for example cytochrome bc 1 complex (38), sulfite reductase (39), and, to a lesser extent, the components of the bovine adrenodoxin reductase⅐adrenodoxin eT complex (40). Our own studies have illustrated that ETF also undergoes large-scale conformational change on electron transfer complex formation (25)(26)(27), as illustrated by the "rearrangement" step in Reaction 2. The results we present here, consistent with our earlier conclusions (18), suggest that this rearrangement does not lead to the thermodynamically most stable state (which is formed too slowly) but to one or more (more rapidly formed) metastable states that are productive electron transfer complexes.…”

Section: Electron Transfer Can Occur In Metastable Tmadh⅐etfmentioning

confidence: 99%

“…We have demonstrated using small-angle x-ray scattering methods that domain II is conformationally mobile and that this flexibility produces an ensemble of ETF structures, only a subset of which can dock onto TMADH (26). Recent studies with human ETF have established domain flexibility as a general feature of the ETF family (27), and these dynamic aspects of ETF structure are likely important in optimizing electron transfer rates from redox donor proteins (26,27).…”

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confidence: 99%

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Electron Transfer and Conformational Change in Complexes of Trimethylamine Dehydrogenase and Electron Transferring Flavoprotein

Jones¹,

Talfournier²,

Bobrov³

et al. 2002

Journal of Biological Chemistry

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The trimethylamine dehydrogenase-electron transferring flavoprotein (TMADH⅐ETF) electron transfer complex has been studied by fluorescence and absorption spectroscopies. These studies indicate that a series of conformational changes occur during the assembly of the TMADH⅐ETF electron transfer complex and that the kinetics of assembly observed with mutant TMADH (Y442F/L/G) or ETF (␣R237A) complexes are much slower than are the corresponding rates of electron transfer in these complexes. This suggests that electron transfer does not occur in the thermodynamically most favorable state (which takes too long to form), but that one or more metastable states (which are formed more rapidly) are competent in transferring electrons from TMADH to ETF. Additionally, fluorescence spectroscopy studies of the TMADH⅐ETF complex indicate that ETF undergoes a stable conformational change (termed structural imprinting) when it interacts transiently with TMADH to form a second, distinct, structural form. The mutant complexes compromise imprinting of ETF, indicating a dependence on the native interactions present in the wild-type complex. The imprinted form of semiquinone ETF exhibits an enhanced rate of electron transfer to the artificial electron acceptor, ferricenium. Overall molecular conformations as probed by smallangle x-ray scattering studies are indistinguishable for imprinted and non-imprinted ETF, suggesting that changes in structure likely involve confined reorganizations within the vicinity of the FAD. Our results indicate a series of conformational events occur during the assembly of the TMADH⅐ETF electron transfer complex, and that the properties of electron transfer proteins can be affected lastingly by transient interaction with their physiological redox partners. This may have significant implications for our understanding of biological electron transfer reactions in vivo, because ETF encounters TMADH at all times in the cell. Our studies suggest that caution needs to be exercised in extrapolating the properties of in vitro interprotein electron transfer reactions to those occurring in vivo.Trimethylamine dehydrogenase (TMADH, 1 EC 1.5.99.7) from the methylotrophic bacterium Methylophilus methylotrophus (sp. W 3 A 1 ) is a homodimeric iron-sulfur flavoprotein that forms an electron transfer complex with electron transferring flavoprotein (ETF (1)). Each subunit of TMADH (molecular mass ϳ 83 kDa) contains a covalently linked 6-S-cysteinyl FMN cofactor, a 4Fe-4S center, and a tightly bound ADP of unknown function (2-8). TMADH catalyzes the oxidative demethylation of trimethylamine to form dimethylamine and formaldehyde (Reaction 1),The mechanism of enzyme reduction by trimethylamine has been addressed by stopped-flow spectroscopy in wild-type (9 -11) and mutant (12-15) TMADH enzymes and has recently been reviewed (16). Following substrate reduction of TMADH, electrons are transferred sequentially from the FMN cofactor to the 4Fe-4S center and, subsequently, in an interprotein electron transfer reaction to the FAD of ...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Electron Transfer Can Occur In Metastable Tmadh⅐etfmentioning

confidence: 99%

mentioning

confidence: 99%

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Electron Transfer and Conformational Change in Complexes of Trimethylamine Dehydrogenase and Electron Transferring Flavoprotein

Jones¹,

Talfournier²,

Bobrov³

et al. 2002

Journal of Biological Chemistry

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“…Recent models constructed using the known crystal structures of human ETF and its partner human MCAD have suggested that electron transfer from MCAD to ETF requires rotational movement of the ETF FAD domain (7). Also, the recent structure determination of ETF from the bacterium Methylophilus methylotrophus in complex with its partner trimethylamine dehydrogenase (TMADH) reveals a highly dynamic proteinprotein interface in which the FAD domain of ETF samples the available space within the complex (8).…”

mentioning

confidence: 99%

Extensive Domain Motion and Electron Transfer in the Human Electron Transferring Flavoprotein·Medium Chain Acyl-CoA Dehydrogenase Complex

Toogood

Thiel

Basran

et al. 2004

Journal of Biological Chemistry

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137

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The crystal structure of the human electron transferring flavoprotein (ETF)⅐medium chain acyl-CoA dehydrogenase (MCAD) complex reveals a dual mode of protein-protein interaction, imparting both specificity and promiscuity in the interaction of ETF with a range of structurally distinct primary dehydrogenases. ETF partitions the functions of partner binding and electron transfer between (i) the recognition loop, which acts as a static anchor at the ETF⅐MCAD interface, and (ii) the highly mobile redox active FAD domain. Together, these enable the FAD domain of ETF to sample a range of conformations, some compatible with fast interprotein electron transfer. Disorders in amino acid or fatty acid catabolism can be attributed to mutations at the protein-protein interface. Crucially, complex formation triggers mobility of the FAD domain, an induced disorder that contrasts with general models of protein-protein interaction by induced fit mechanisms. The subsequent interfacial motion in the MCAD⅐ETF complex is the basis for the interaction of ETF with structurally diverse protein partners. Solution studies using ETF and MCAD with mutations at the protein-protein interface support this dynamic model and indicate ionic interactions between MCAD Glu 212 and ETF Arg␣ 249 are likely to transiently stabilize productive conformations of the FAD domain leading to enhanced electron transfer rates between both partners.

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Thermal Fluctuations Determine the Electron‐Transfer Rates of Cytochrome c in Electrostatic and Covalent Complexes

Martí

Martín

et al. 2010

ChemPhysChem

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The heterogeneous electron-transfer (ET) reaction of cytochrome c (Cyt-c) electrostatically or covalently immobilized on electrodes coated with self-assembled monolayers (SAMs) of omega-functionalized alkanethiols is analyzed by surface-enhanced resonance Raman (SERR) spectroscopy and molecular dynamics (MD) simulations. Electrostatically bound Cyt-c on pure carboxyl-terminated and mixed carboxyl/hydroxyl-terminated SAMs reveals the same distance dependence of the rate constants, that is, electron tunneling at long distances and a regime controlled by the protein orientational distribution and dynamics that leads to a nearly distance-independent rate constant at short distances. Qualitatively, the same behavior is found for covalently bound Cyt-c, although the apparent ET rates in the plateau region are lower since protein mobility is restricted due to formation of amide bonds between the protein and the SAM. The experimental findings are consistent with the results of MD simulations indicating that thermal fluctuations of the protein and interfacial solvent molecules can effectively modulate the electron tunneling probability.

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Protein Dynamics Enhance Electronic Coupling in Electron Transfer Complexes

Cited by 39 publications

References 37 publications

Electron Transfer and Conformational Change in Complexes of Trimethylamine Dehydrogenase and Electron Transferring Flavoprotein

Electron Transfer and Conformational Change in Complexes of Trimethylamine Dehydrogenase and Electron Transferring Flavoprotein

Extensive Domain Motion and Electron Transfer in the Human Electron Transferring Flavoprotein·Medium Chain Acyl-CoA Dehydrogenase Complex

Thermal Fluctuations Determine the Electron‐Transfer Rates of Cytochrome c in Electrostatic and Covalent Complexes

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