Protonation-State-Dependent Communication in Cytochrome c Oxidase

Helabad, Mahdi Bagherpoor; Ghane, Tahereh; Reidelbach, Marco; Woelke, Anna Lena; Knapp, Ernst Walter; Imhof, Petra

doi:10.1016/j.bpj.2017.07.005

Cited by 6 publications

(5 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The model setup for the protein embedded in a solvated lipid bilayer follows the same protocol as described in [30] and also employed by some of us in previous MD simulation of CcOin another, Pr → F redox state [33]. The model consists of subunits I and II of CcO from R. sphaeroides(based on a crystal structure with PDB entry 2GSM [34,35]) embedded in a lipid bilayer of phosphatidylcholines and solvated in TIP3P water [36] in a tetragonal box of size (x = y = 96 Å, z = 124 Å).…”

Section: Molecular Dynamics Simulations Model Setupmentioning

confidence: 99%

“…Hydrogen bonds were defined by geometric criteria, i.e., the donor-acceptor distance must not exceed 3.5 Å and the donor-hydrogen-acceptor (D-H• • • A) angle must not deviate more than 35 degrees from linear. These are the same criteria as we have used in the analysis of previous MD simulations of CcO [33,46]. A directed hydrogen bond is defined as pointing from the donor to the acceptor residue.…”

Section: Analysis 231 Structural Parametersmentioning

confidence: 99%

“…In the "down" models, K362 does not flip up, indicating that in the rather short MD simulations used to sample the water positions and hydrogen bonded connections such a transition is not feasible. In longer simulations [30,33], such transitions are observed, rendering proton transport by K362 as a carrier a possible, but not the only route. Instead, K362's role can be regarded as a valve, separating the upper and lower parts of the K-channel and, in an "up" position, preventing proton transport back to the bottom of the channel but possibly also the translocation of another proton before the next step in the catalytic cycle.…”

Section: Interplay Of K362 Conformation Hydrogen-bonded Connections and Proton Transfer Probabilitiesmentioning

confidence: 99%

See 2 more Smart Citations

Protonation Dynamics in the K-Channel of Cytochrome c Oxidase Estimated from Molecular Dynamics Simulations

2021

Self Cite

View full text Add to dashboard Cite

Proton transfer reactions are one of the most fundamental processes in biochemistry. We present a simplistic approach for estimating proton transfer probabilities in a membrane protein, cytochrome c oxidase. We combine short molecular dynamics simulations at discrete protonation states with a Monte Carlo approach to exchange between those states. Requesting for a proton transfer the existence of a hydrogen-bonded connection between the two source and target residues of the exchange,restricts the acceptance of transfers to only those in which a proton-relay is possible. Together with an analysis of the hydrogen-bonded connectivity in one of the proton-conducting channels of cytochrome c oxidase, this approach gives insight into the protonation dynamics of the hydrogen-bonded networks. The connectivity and directionality of the networks are coupled to the conformation of an important protein residue in the channel, K362, rendering proton transfer in the entire channel feasible in only one of the two major conformations. Proton transport in the channel can thus be regulated by K362 not only through its possible role as a proton carrier itself, but also by allowing or preventing proton transport via water residues.

show abstract

Section: Molecular Dynamics Simulations Model Setupmentioning

confidence: 99%

Section: Analysis 231 Structural Parametersmentioning

confidence: 99%

Section: Interplay Of K362 Conformation Hydrogen-bonded Connections and Proton Transfer Probabilitiesmentioning

confidence: 99%

See 1 more Smart Citation

Protonation Dynamics in the K-Channel of Cytochrome c Oxidase Estimated from Molecular Dynamics Simulations

2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The proposed D-channel gate, however, is formed by an asparagine, rendering conformational changes due to a direct protonation hardly probable. Instead, MD simulations revealed a correlation between the conformation of the gate and the protonation state of other residues inside the channel [15, 16]. Furthermore, MD simulations revealed a correlation between the channel hydration and the protonation state of individual residues [17, 18].…”

Section: Introductionmentioning

confidence: 99%

“…In the case of proton translocations through proton transfer channels, the number of degrees of freedom (DOFs) to sample, corresponding to critical channel residues and intra-channel water molecules, is already problematic. However, investigations in CcO as well as NADH dehydrogenase furthermore suggest, that the environment of the proton transfer channel is able to affect intra-channel properties [15, 17, 18]. Hence, thorough investigations of the proton translocation should also include the channel environment.…”

Section: Introductionmentioning

confidence: 99%

Prediction of perturbed proton transfer networks

2018

Self Cite

View full text Add to dashboard Cite

The transfer of protons through proton translocating channels is a complex process, for which direct samplings of different protonation states and side chain conformations in a transition network calculation provide an efficient, bias-free description. In principle, a new transition network calculation is required for every unsampled change in the system of interest, e.g. an unsampled protonation state change, which is associated with significant computational costs. Transition networks void of or including an unsampled change are termed unperturbed or perturbed, respectively. Here, we present a prediction method, which is based on an extensive coarse-graining of the underlying transition networks to speed up the calculations. It uses the minimum spanning tree and a corresponding sensitivity analysis of an unperturbed transition network as initial guess and refinement parameter for the determination of an unknown, perturbed transition network. Thereby, the minimum spanning tree defines a sub-network connecting all nodes without cycles and minimal edge weight sum, while the sensitivity analysis analyzes the stability of the minimum spanning tree towards individual edge weight reductions. Using the prediction method, we are able to reduce the calculation costs in a model system by up to 80%, while important network properties are maintained in most predictions.

show abstract

Hydrogen-Bonded Network and Water Dynamics in the D-channel of Cytochrome c Oxidase

et al. 2018

View full text Add to dashboard Cite

Proton transfer in cytochrome c oxidase (CcO) from the cellular inside to the binuclear redox centre as well as proton pumping through the membrane takes place through proton entrance via two distinct pathways, the D- and K-channel. Both channels show a dependence of their hydration level on the protonation states of their key residues, K362 for the K-channel, and E286 or D132 for the D-channel. In the oxidative half of CcO's catalytic cycle the D-channel is the proton-conducting path. For this channel, an interplay of protonation state of the D-channel residues with the water and hydrogen-bond dynamics has been observed in molecular dynamics simulations of the CcO protein, embedded in a lipid bi-layer, modelled in different protonation states. Protonation of residue E286 at the end of the D-channel results in a hydrogen-bonded network pointing from E286 to N139, that is against proton transport, and favouring N139 conformations which correspond to a closed asparagine gate (formed by residues N121 and N139). Consequently, the hydration level is lower than with unprotonated E286. In those models, the Asn gate is predominantly open, allowing water molecules to pass and thus increase the hydration level. The hydrogen-bonded network in these states exhibits longer life times of the Asn residues with water than other models and shows the D-channel to be traversable from the entrance, D132, to exit, E286. The D-channel can thus be regarded as auto-regulated with respect to proton transport, allowing proton passage only when required, that is the proton is located at the lower part of the D-channel (D132 to Asn gate) and not at the exit (E286).

show abstract

Protonation-State-Dependent Communication in Cytochrome c Oxidase

Cited by 6 publications

References 40 publications

Protonation Dynamics in the K-Channel of Cytochrome c Oxidase Estimated from Molecular Dynamics Simulations

Protonation Dynamics in the K-Channel of Cytochrome c Oxidase Estimated from Molecular Dynamics Simulations

Prediction of perturbed proton transfer networks

Hydrogen-Bonded Network and Water Dynamics in the D-channel of Cytochrome c Oxidase

Contact Info

Product

Resources

About