Dynamics of the molecular motor F0 and its interaction with the membrane under external electric fields
Date Issued
2010
Date
2010
Author(s)
Lin, Yang-Shan
Abstract
The membrane-bound component F0, which is one major component of the F0F1-ATP synthase, works as a rotary motor and plays the central role of driving the F1 component to transform chemi-osmotic energy into ATP synthesis. We have conducted molecular dynamics simulations of a b2-free F0 protein in the 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) lipid bilayer for tens of nanoseconds with two different protonation states of the cAsp61 residue at the interface of the a-c complex in the absence of electric fields and under electric fields of ±0.03 V/nm across this membrane. Principal component analysis (PCA) revealed that the all-protonated Asp61 cases indeed exhibit larger motion and the external electric fields strongly influence the dynamics of F0. Correlation map analysis indicated that the correlated motions of residues in the interface of the a-c complex were significantly reduced by external electric fields. When Asp61 were protonated, the Ala24 and Ile28 of the N-terminal helix rotated about its axis by 30°. This rotation induced by electrostatic interaction between N-terminal helix and C12 subunit may lead the conformational changes in the C-terminal helix which are important for the rotation of c ring. Van der Waals and Coulomb interactions between a- and c-subunit were calculated to confirm the former plays the dominant role in stabilizing two subunits which are hydrophobic. We also applied hydrogen bonds networks analysis to the residues on three individual proton translocation pathways to see whether the hydrogen bonds formed between these residues. Direct observation of the aqueous-accessible region within the a subunit is used to support there are water molecules in this region. The intrinsic pKa values of Asp61, Lys203 and Glu219 are supported by the experimental data. The deuterium order parameter (SCD) profile calculated by averaging all the lipids in the F0-bound bilayer was not very different from that of the pure bilayer system, which agrees with recent 2H solid-state NMR experiments (Kobayahi et al, Biophys. J., 94, 2008). However, by delineating the lipid properties according to their vicinity to F0, we found that the SCD profiles of different lipid shells are prominently different. Lipids close to F0 formed a more ordered structure. Similarly, the lateral diffusion of lipids on the membrane surface also followed a shell-dependent behavior. The lipids in the proximity of F0 exhibited very significantly reduced diffusional motion. The numerical value of SCD was anti-correlated with that of the diffusion coefficient, i.e., the more ordered lipid structures led to slower lipid diffusion. These findings not only be useful to understand the dynamics of F0 related to the protonation state and electric fields, but may shed some light to the interactions between the motor F0 and its surrounding lipids under physiological condition, which could help to rationalize its extraordinary energy conversion efficiency.
Subjects
molecular motor
F0F1-ATP synthase
lipid shells
molecular dynamics simulation
Type
thesis
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