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Mechanical energy transduction in F1-ATPase
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Rainer Böckmann and Helmut Grubmüller
ATP synthase is believed to be a rotatory engine driven by proton- or sodium-motive force and thus the smallest molecular motor known. The proton flow through the membrane portion F0 drives the synthesis of ATP in the three active sites of the headpiece, F1. The energy transfer from the F0 portion to the active sites in the F1 portion is thought to be mediated by the γ-subunit, an asymmetric, coiled-coil shaft. This subunit acts like a crankshaft within the trigonal
(αβ)3 substructure of the F1 headpiece. It has been shown that translocation of 3-4 protons through the cell membrane is required for the synthesis and release of one ATP in an active site of the F1 headpiece.
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The goal of the present project is to study ATPase by molecular dynamics (MD) simulations [1], especially the energy transfer, the stability of the γ subunit and its role in the synthesis mechanism as well as conformational changes associated with the binding of ADP and phosphate and the release of ATP.
We study both the stability of the isolated Gamma-subunit against torsion and its ability of energy storage as well as the energy transfer in the full ATPase.
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In the simulations we add a rotating harmonic potential to 40-60 backbone atoms at the lower part of the γ-subunit (see figure on the right). The simulations are carried out using the MD program EGO [1] starting from the crystal structure within a droplet of water molecules.
First results indicate that the γ-subunit as part of the ATPase can not withstand the necessary applied torques. Accordingly, the γ-subunit may unfold/refold during rotation.
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References
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- M.Eichinger, H. Grubmüller and H.Heller. User Manual for EGO_VIII, Release 1.0 (1995) electronic access: EGO: A Parallel Program for Molecular Dynamics Simulations of Biomolecules
[LINK]
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R. A. Böckmann and H. Grubmüller. Conformational dynamics of the F1-ATPase ß-subunit: A molecular dynamics study. Biophys. J. 85: 1482-1491 (2003)
[pdf]
[cover]
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R. Böckmann and H. Grubmüller. Nanoseconds molecular dynamics simulation of primary mechanical energy transfer steps in F1-ATP synthase. Nature Struct. Biol. 9: 198-202 (2002)
[pdf]
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See also
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Czub J, and Grubmüller H.
Torsional elasticity and energetics of F1-ATPase.
PNAS 108; 7408-7413 (2011)
[pdf]
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Kutzner C, Czub J, and Grubmüller H.
Keep it Flexible: Driving Macromolecular Rotary Motions in Atomistic Simulations with GROMACS.
J. Chem Theory and Comp. 7: 1381-1393 (2011)
[pdf]
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