TY - JOUR
T1 - Mitochondrial ATP synthase
T2 - Crystal structure of the catalytic F 1 unit in a vanadate-induced transition-like state and implications for mechanism
AU - Chen, Chen
AU - Saxena, Ajay K.
AU - Simcoke, William N.
AU - Garboczi, David N.
AU - Pedersen, Peter L.
AU - Ko, Young H.
PY - 2006/5/12
Y1 - 2006/5/12
N2 - ATP synthesis from ADP, Pi, and Mg2+ takes place in mitochondria on the catalytic F1 unit (α3β 3γδε) of the ATP synthase complex (F 0F1), a remarkable nanomachine that interconverts electrochemical and mechanical energy, producing the high energy terminal bond of ATP. In currently available structural models of F1, the P-loop (amino acid residues 156GGAGVGKT163) contributes to substrate binding at the β subunit catalytic sites. Here, we report the first transition state-like structure of F1 (ADP·V i·Mg·F1) from rat liver that was crystallized with the phosphate (Pi) analog vanadate (VO 43- or Vi). Compared with earlier "ground state" structures, this new F1 structure reveals that the active site region has undergone significant remodeling. P-loop residue alanine 158 is located much closer to Vi than it is to Pi in a previous structural model. No significant movements of P-loop residues of the α subunit were observed at its analogous but noncatalytic sites. Under physiological conditions, such active site remodeling involving the small hydrophobic alanine residue may promote ATP synthesis by lowering the local dielectric constant, thus facilitating the dehydration of ADP and Pi. This new crystallographic study provides strong support for the catalytic mechanism of ATP synthesis deduced from earlier biochemical studies of liver F1 conducted in the presence of Vi (Ko, Y. H., Bianchet, M., Amzel, L. M., and Pedersen, P. L. (1997) J. Biol. Chem. 272, 18875-18881; Ko, Y. H., Hong, S., and Pedersen, P. L. (1999) J. Biol. Chem. 274, 28853-28856).
AB - ATP synthesis from ADP, Pi, and Mg2+ takes place in mitochondria on the catalytic F1 unit (α3β 3γδε) of the ATP synthase complex (F 0F1), a remarkable nanomachine that interconverts electrochemical and mechanical energy, producing the high energy terminal bond of ATP. In currently available structural models of F1, the P-loop (amino acid residues 156GGAGVGKT163) contributes to substrate binding at the β subunit catalytic sites. Here, we report the first transition state-like structure of F1 (ADP·V i·Mg·F1) from rat liver that was crystallized with the phosphate (Pi) analog vanadate (VO 43- or Vi). Compared with earlier "ground state" structures, this new F1 structure reveals that the active site region has undergone significant remodeling. P-loop residue alanine 158 is located much closer to Vi than it is to Pi in a previous structural model. No significant movements of P-loop residues of the α subunit were observed at its analogous but noncatalytic sites. Under physiological conditions, such active site remodeling involving the small hydrophobic alanine residue may promote ATP synthesis by lowering the local dielectric constant, thus facilitating the dehydration of ADP and Pi. This new crystallographic study provides strong support for the catalytic mechanism of ATP synthesis deduced from earlier biochemical studies of liver F1 conducted in the presence of Vi (Ko, Y. H., Bianchet, M., Amzel, L. M., and Pedersen, P. L. (1997) J. Biol. Chem. 272, 18875-18881; Ko, Y. H., Hong, S., and Pedersen, P. L. (1999) J. Biol. Chem. 274, 28853-28856).
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U2 - 10.1074/jbc.M513369200
DO - 10.1074/jbc.M513369200
M3 - Article
C2 - 16531409
AN - SCOPUS:33744949740
SN - 0021-9258
VL - 281
SP - 13777
EP - 13783
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 19
ER -