Insights on the proton translocation pathways in FоF1-ATP synthase using molecular dynamics simulations

Ivontsin, Leonid A.; Mashkovtseva, Elena V.; Nartsissov, Yaroslav R.

doi:10.1016/j.abb.2022.109135

Cited by 5 publications

(9 citation statements)

References 34 publications

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“…Water molecules penetrated into the inlet half-channel up to these amino acids, forming very branched chains of hydrogen bonds, through which the proton could easily reach them from the periplasm, for example, by the Grotthuss mechanism. Remarkably, in the model POPC membrane we observed two structural water molecules (W2 and W3) ( Figure 5 a) which continued the proton transfer chain [ 33 ], since there was no direct transfer from a Glu219 to a Asp119/ a His245. Whereas, in in vivo membranes and simulated bacterial stress with CL, W2 and W3 still existed, but a possible direct transfer was observed.…”

Section: Resultsmentioning

confidence: 99%

“…To describe their dynamics, the root mean square fluctuation (RMSF) of the amino acid side chain and the angle χ between the side chain and the axis of the alpha helix were calculated ( Figure 3 ). Amino acid side chains’ stable spatial positions were determined as positions having average fluctuation amplitudes on par with the magnitude of atoms’ thermal fluctuations [ 33 ]. Regardless of the CL presence in the membrane, stable spatial positions of a Asn214 were observed.…”

Section: Resultsmentioning

confidence: 99%

“…In the model POPC membrane, proton transfer from a Asn214 and a Gln252 was carried out to c Asp61 only via the structural water molecule W1 that we discovered in all simulations [ 33 ] ( Figure 5 c). In the presence of CL, instead of the single favorable position of the structural molecule of water W1, a greater conformational freedom of water around c Asp61 was found.…”

Section: Resultsmentioning

confidence: 99%

“… Water accessibility of the inlet half-channel obtained from simulations in the model POPC membrane [ 33 ] ( a ) and an in vivo membrane containing 25% CL ( b ). The separate ( a ) and aggregate ( b ) aqueous lacunae are labelled as a red surface, cardiolipins are drawn as licorice.…”

Section: Figurementioning

confidence: 99%

“…The structural dynamics of significant polar amino acids and protein hydration have been investigated. Conservative localizations of structural water molecule clusters critical for proton transport have been established [ 33 ]. However, the study of membrane lipid composition’s influence on the structure of proton half-channels is especially interesting.…”

Section: Introductionmentioning

confidence: 99%

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Membrane Lipid Composition Influences the Hydration of Proton Half-Channels in FoF1-ATP Synthase

Ivontsin,

Mashkovtseva,

Nartsissov

2023

Life

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The membrane lipid composition plays an important role in the regulation of membrane protein activity. To probe its influence on proton half-channels’ structure in FoF1-ATP synthase, we performed molecular dynamics simulations with the bacterial protein complex (PDB ID: 6VWK) embedded in three types of membranes: a model POPC, a lipid bilayer containing 25% (in vivo), and 75% (bacterial stress) of cardiolipin (CL). The structure proved to be stable regardless of the lipid composition. The presence of CL increased the hydration of half-channels. The merging of two water cavities at the inlet half-channel entrance and a long continuous chain of water molecules directly to cAsp61 from the periplasm were observed. Minor conformational changes in half-channels with the addition of CL caused extremely rare direct transitions between aGlu219-aAsp119, aGlu219-aHis245, and aGln252-cAsp61. Deeper penetration of water molecules (W1–W3) also increased the proton transport continuity. Stable spatial positions of significant amino acid (AA) residue aAsn214 were found under all simulation conditions indicate a prevailing influence of AA-AA or AA-W interactions on the side-chain dynamics. These results allowed us to put forward a model of the proton movement in ATP synthases under conditions close to in vivo and to evaluate the importance of membrane composition in simulations.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Membrane Lipid Composition Influences the Hydration of Proton Half-Channels in FoF1-ATP Synthase

Ivontsin,

Mashkovtseva,

Nartsissov

2023

Life

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Ion-driven rotary membrane motors: From structure to function

Martin,

Santiveri,

et al. 2024

Current Opinion in Structural Biology

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The Ancestral Shape of the Access Proton Path of Mitochondrial ATP Synthases Revealed by a Split Subunit-a

Wong

Zı́ková

Gahura

2023

Molecular Biology and Evolution

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The passage of protons across membranes through F1Fo-ATP synthases spins their rotors and drives synthesis of ATP. While the principle of torque generation by proton transfer is known, the mechanisms and routes of proton access and release and their evolution are not fully understood. Here, we show that the entry site and path of protons in the lumenal half-channel of mitochondrial ATP synthases are largely defined by a short N-terminal α-helix of subunit-a. In Trypanosoma brucei and other Euglenozoa, the α-helix is part of another polypeptide chain that is a product of subunit-a gene fragmentation. This α-helix and other elements forming the proton pathway are widely conserved across eukaryotes and in Alphaproteobacteria, the closest extant relatives of mitochondria, but not in other bacteria. The α-helix blocks one of two proton routes found in Escherichia coli, resulting in the single proton entry site in mitochondrial and alphaproteobacterial ATP synthases. Thus, the shape of the access half-channel predates eukaryotes and originated in the lineage from which mitochondria evolved by endosymbiosis.

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Insights on the proton translocation pathways in FоF1-ATP synthase using molecular dynamics simulations

Cited by 5 publications

References 34 publications

Membrane Lipid Composition Influences the Hydration of Proton Half-Channels in FoF1-ATP Synthase

Membrane Lipid Composition Influences the Hydration of Proton Half-Channels in FoF1-ATP Synthase

Ion-driven rotary membrane motors: From structure to function

The Ancestral Shape of the Access Proton Path of Mitochondrial ATP Synthases Revealed by a Split Subunit-a

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