Limits...
ATP synthase: from single molecule to human bioenergetics.

Kagawa Y - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Bottom Line: F(o)F(1) reconstituted into a lipid membrane is capable of ATP synthesis driven by H(+) flux.As the basic structures of F(1) (alpha(3)beta(3)gammadeltaepsilon) and F(o) (ab(2)c(10)) are ubiquitous, stable thermophilic F(o)F(1) (TF(o)F(1)) has been used to elucidate molecular mechanisms, while human F(1)F(o) (HF(1)F(o)) has been used to study biomedical significance.In contrast to the single operon of TF(o)F(1), HF(o)F(1) is encoded by both nuclear DNA with introns and mitochondrial DNA.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Tochigi, Japan. kagawa@eiyo.ac.jp

ABSTRACT
ATP synthase (F(o)F(1)) consists of an ATP-driven motor (F(1)) and a H(+)-driven motor (F(o)), which rotate in opposite directions. F(o)F(1) reconstituted into a lipid membrane is capable of ATP synthesis driven by H(+) flux. As the basic structures of F(1) (alpha(3)beta(3)gammadeltaepsilon) and F(o) (ab(2)c(10)) are ubiquitous, stable thermophilic F(o)F(1) (TF(o)F(1)) has been used to elucidate molecular mechanisms, while human F(1)F(o) (HF(1)F(o)) has been used to study biomedical significance. Among F(1)s, only thermophilic F(1) (TF(1)) can be analyzed simultaneously by reconstitution, crystallography, mutagenesis and nanotechnology for torque-driven ATP synthesis using elastic coupling mechanisms. In contrast to the single operon of TF(o)F(1), HF(o)F(1) is encoded by both nuclear DNA with introns and mitochondrial DNA. The regulatory mechanism, tissue specificity and physiopathology of HF(o)F(1) were elucidated by proteomics, RNA interference, cytoplasts and transgenic mice. The ATP synthesized daily by HF(o)F(1) is in the order of tens of kilograms, and is primarily controlled by the brain in response to fluctuations in activity.

Show MeSH

Related in: MedlinePlus

Crystals of TF1 and α3β3, and X-ray crystallography data for the catalytic center of F1. A. Catalytic center of the β subunit of BF1 (black text indicates residue number)9) and TF1 (red text indicates residue numbers).12) Except for αR373 and αS344, all of the amino acid residues are present in β. Residues 159–164 are part of the P-loop surrounding the triphosphate residue of ATP. B. Crystals of TF1.70) C. Crystals of α3β3.71) D. Top view of the crystallographic structure of α3β3.71)
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3066536&req=5

fig05: Crystals of TF1 and α3β3, and X-ray crystallography data for the catalytic center of F1. A. Catalytic center of the β subunit of BF1 (black text indicates residue number)9) and TF1 (red text indicates residue numbers).12) Except for αR373 and αS344, all of the amino acid residues are present in β. Residues 159–164 are part of the P-loop surrounding the triphosphate residue of ATP. B. Crystals of TF1.70) C. Crystals of α3β3.71) D. Top view of the crystallographic structure of α3β3.71)

Mentions: Chemical and genetic modification of residues in F1 revealed a nucleotide-binding P-loop (-GGAGVGKT-; thermophilic β158–165 corresponds to bovine β156–163) (Figs. 4, 5A).7,9,12,19,54) Long before the X-ray crystallographic elucidation of the P-loop,9) site-directed mutagenesis of the TF1 gene20) to induce thermophilic βK164I and thermophilic αK175I, identified an essential role for lysine residues in the catalysis (Fig. 5A, red letters).20) The proton abstracting thermophilic βE190 (Fig. 5A) localized in the GER-loop (-VGER-) (Fig. 4)7,19,54) was also predicted by TF1 mutagenesis producing thermophilic βE190Q.67) These mutant TF1 subunits produced an α3β3γ complex that was suitable for experiments on torque-driven ATP synthesis.64) Species-specific residues (black letters in Fig. 4) may have phylogenic components, including thermophilic loops (-ARNENEV-) (Fig. 4, first line I′) that render TF1 stable.19) Since determining the nucleotide sequence of TFoF1,7,12,19) numerous rotating ATP synthases of thermophilic F-type or V-type (vacuolar ATPase) have been sequence and characterized.65,68)


ATP synthase: from single molecule to human bioenergetics.

Kagawa Y - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Crystals of TF1 and α3β3, and X-ray crystallography data for the catalytic center of F1. A. Catalytic center of the β subunit of BF1 (black text indicates residue number)9) and TF1 (red text indicates residue numbers).12) Except for αR373 and αS344, all of the amino acid residues are present in β. Residues 159–164 are part of the P-loop surrounding the triphosphate residue of ATP. B. Crystals of TF1.70) C. Crystals of α3β3.71) D. Top view of the crystallographic structure of α3β3.71)
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066536&req=5

fig05: Crystals of TF1 and α3β3, and X-ray crystallography data for the catalytic center of F1. A. Catalytic center of the β subunit of BF1 (black text indicates residue number)9) and TF1 (red text indicates residue numbers).12) Except for αR373 and αS344, all of the amino acid residues are present in β. Residues 159–164 are part of the P-loop surrounding the triphosphate residue of ATP. B. Crystals of TF1.70) C. Crystals of α3β3.71) D. Top view of the crystallographic structure of α3β3.71)
Mentions: Chemical and genetic modification of residues in F1 revealed a nucleotide-binding P-loop (-GGAGVGKT-; thermophilic β158–165 corresponds to bovine β156–163) (Figs. 4, 5A).7,9,12,19,54) Long before the X-ray crystallographic elucidation of the P-loop,9) site-directed mutagenesis of the TF1 gene20) to induce thermophilic βK164I and thermophilic αK175I, identified an essential role for lysine residues in the catalysis (Fig. 5A, red letters).20) The proton abstracting thermophilic βE190 (Fig. 5A) localized in the GER-loop (-VGER-) (Fig. 4)7,19,54) was also predicted by TF1 mutagenesis producing thermophilic βE190Q.67) These mutant TF1 subunits produced an α3β3γ complex that was suitable for experiments on torque-driven ATP synthesis.64) Species-specific residues (black letters in Fig. 4) may have phylogenic components, including thermophilic loops (-ARNENEV-) (Fig. 4, first line I′) that render TF1 stable.19) Since determining the nucleotide sequence of TFoF1,7,12,19) numerous rotating ATP synthases of thermophilic F-type or V-type (vacuolar ATPase) have been sequence and characterized.65,68)

Bottom Line: F(o)F(1) reconstituted into a lipid membrane is capable of ATP synthesis driven by H(+) flux.As the basic structures of F(1) (alpha(3)beta(3)gammadeltaepsilon) and F(o) (ab(2)c(10)) are ubiquitous, stable thermophilic F(o)F(1) (TF(o)F(1)) has been used to elucidate molecular mechanisms, while human F(1)F(o) (HF(1)F(o)) has been used to study biomedical significance.In contrast to the single operon of TF(o)F(1), HF(o)F(1) is encoded by both nuclear DNA with introns and mitochondrial DNA.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Tochigi, Japan. kagawa@eiyo.ac.jp

ABSTRACT
ATP synthase (F(o)F(1)) consists of an ATP-driven motor (F(1)) and a H(+)-driven motor (F(o)), which rotate in opposite directions. F(o)F(1) reconstituted into a lipid membrane is capable of ATP synthesis driven by H(+) flux. As the basic structures of F(1) (alpha(3)beta(3)gammadeltaepsilon) and F(o) (ab(2)c(10)) are ubiquitous, stable thermophilic F(o)F(1) (TF(o)F(1)) has been used to elucidate molecular mechanisms, while human F(1)F(o) (HF(1)F(o)) has been used to study biomedical significance. Among F(1)s, only thermophilic F(1) (TF(1)) can be analyzed simultaneously by reconstitution, crystallography, mutagenesis and nanotechnology for torque-driven ATP synthesis using elastic coupling mechanisms. In contrast to the single operon of TF(o)F(1), HF(o)F(1) is encoded by both nuclear DNA with introns and mitochondrial DNA. The regulatory mechanism, tissue specificity and physiopathology of HF(o)F(1) were elucidated by proteomics, RNA interference, cytoplasts and transgenic mice. The ATP synthesized daily by HF(o)F(1) is in the order of tens of kilograms, and is primarily controlled by the brain in response to fluctuations in activity.

Show MeSH
Related in: MedlinePlus