How Subunit Coupling Produces the Gamma-subunit Rotary Motion in F1-ATPase

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Jan 25

PMID 18216260

Citations 53

Authors

Jingzhi Pu

Martin Karplus

Affiliations

Soon will be listed here.

Abstract

F(o)F(1)-ATP synthase manufactures the energy "currency," ATP, of living cells. The soluble F(1) portion, called F(1)-ATPase, can act as a rotary motor, with ATP binding, hydrolysis, and product release, inducing a torque on the gamma-subunit. A coarse-grained plastic network model is used to show at a residue level of detail how the conformational changes of the catalytic beta-subunits act on the gamma-subunit through repulsive van der Waals interactions to generate a torque that drives unidirectional rotation, as observed experimentally. The simulations suggest that the calculated 85 degrees substep rotation is driven primarily by ATP binding and that the subsequent 35 degrees substep rotation is produced by product release from one beta-subunit and a concomitant binding pocket expansion of another beta-subunit. The results of the simulation agree with single-molecule experiments [see, for example, Adachi K, et al. (2007) Cell 130:309-321] and support a tri-site rotary mechanism for F(1)-ATPase under physiological condition.

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References

van der Vaart A, Karplus M . Simulation of conformational transitions by the restricted perturbation-targeted molecular dynamics method. J Chem Phys. 2005; 122(11):114903. DOI: 10.1063/1.1861885. View

Itoh H, Takahashi A, Adachi K, Noji H, Yasuda R, Yoshida M . Mechanically driven ATP synthesis by F1-ATPase. Nature. 2004; 427(6973):465-8. DOI: 10.1038/nature02212. View

Kabaleeswaran V, Puri N, Walker J, Leslie A, Mueller D . Novel features of the rotary catalytic mechanism revealed in the structure of yeast F1 ATPase. EMBO J. 2006; 25(22):5433-42. PMC: 1636620. DOI: 10.1038/sj.emboj.7601410. View

Bockmann R, Grubmuller H . Nanoseconds molecular dynamics simulation of primary mechanical energy transfer steps in F1-ATP synthase. Nat Struct Biol. 2002; 9(3):198-202. DOI: 10.1038/nsb760. View

Bowler M, Montgomery M, Leslie A, Walker J . Ground state structure of F1-ATPase from bovine heart mitochondria at 1.9 A resolution. J Biol Chem. 2007; 282(19):14238-42. DOI: 10.1074/jbc.M700203200. View

Menz R, Walker J, Leslie A . Structure of bovine mitochondrial F(1)-ATPase with nucleotide bound to all three catalytic sites: implications for the mechanism of rotary catalysis. Cell. 2001; 106(3):331-41. DOI: 10.1016/s0092-8674(01)00452-4. View

Junge W, Lill H, Engelbrecht S . ATP synthase: an electrochemical transducer with rotatory mechanics. Trends Biochem Sci. 1997; 22(11):420-3. DOI: 10.1016/s0968-0004(97)01129-8. View

Noji H, Yasuda R, Yoshida M, Kinosita Jr K . Direct observation of the rotation of F1-ATPase. Nature. 1997; 386(6622):299-302. DOI: 10.1038/386299a0. View

Gruber G, Capaldi R . Differentiation of catalytic sites on Escherichia coli F1ATPase by laser photoactivated labeling with [3H]-2-Azido-ATP using the mutant beta Glu381Cys:epsilonSer108Cys to identify different beta subunits by their interactions with gamma and epsilon.... Biochemistry. 1996; 35(13):3875-9. DOI: 10.1021/bi952949h. View

10.

Ross J . Energy transfer from adenosine triphosphate. J Phys Chem B. 2006; 110(13):6987-90. DOI: 10.1021/jp0556862. View

11.

Hossain M, Furuike S, Maki Y, Adachi K, Ali M, Huq M . The rotor tip inside a bearing of a thermophilic F1-ATPase is dispensable for torque generation. Biophys J. 2006; 90(11):4195-203. PMC: 1459503. DOI: 10.1529/biophysj.105.079087. View

12.

Schlitter J, Engels M, Kruger P . Targeted molecular dynamics: a new approach for searching pathways of conformational transitions. J Mol Graph. 1994; 12(2):84-9. DOI: 10.1016/0263-7855(94)80072-3. View

13.

Mao H, Weber J . Identification of the betaTP site in the x-ray structure of F1-ATPase as the high-affinity catalytic site. Proc Natl Acad Sci U S A. 2007; 104(47):18478-83. PMC: 2141802. DOI: 10.1073/pnas.0709322104. View

14.

Weber J, Senior A . Catalytic mechanism of F1-ATPase. Biochim Biophys Acta. 1997; 1319(1):19-58. DOI: 10.1016/s0005-2728(96)00121-1. View

15.

BOYER P . The ATP synthase--a splendid molecular machine. Annu Rev Biochem. 1997; 66:717-49. DOI: 10.1146/annurev.biochem.66.1.717. View

16.

Bandyopadhyay S, Allison W . GammaM23K, gammaM232K, and gammaL77K single substitutions in the TF1-ATPase lower ATPase activity by disrupting a cluster of hydrophobic side chains. Biochemistry. 2004; 43(29):9495-501. DOI: 10.1021/bi0493012. View

17.

Bandyopadhyay S, Allison W . The ionic track in the F1-ATPase from the thermophilic Bacillus PS3. Biochemistry. 2004; 43(9):2533-40. DOI: 10.1021/bi036058i. View

18.

Ma J, Flynn T, Cui Q, Leslie A, Walker J, Karplus M . A dynamic analysis of the rotation mechanism for conformational change in F(1)-ATPase. Structure. 2002; 10(7):921-31. DOI: 10.1016/s0969-2126(02)00789-x. View

19.

Greene M, Frasch W . Interactions among gamma R268, gamma Q269, and the beta subunit catch loop of Escherichia coli F1-ATPase are important for catalytic activity. J Biol Chem. 2003; 278(51):51594-8. DOI: 10.1074/jbc.M309948200. View

20.

Gao Y, Yang W, Karplus M . A structure-based model for the synthesis and hydrolysis of ATP by F1-ATPase. Cell. 2005; 123(2):195-205. DOI: 10.1016/j.cell.2005.10.001. View