Proton transfer during class-A GPCR activation: do the CWxP motif and the membrane potential act in concert?

Zhang, Xuejun C.; Zhou, Ye; Cao, Can

doi:10.1007/s41048-018-0056-0

Cited by 7 publications

(5 citation statements)

References 43 publications

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“…In principle, such proton‐titratable groups can also function as pH sensors in the presence of ΔΨ. This type of proton‐titratable residues are likely to be sensitive to point mutations to their corresponding non‐titratable analogous, namely Asp to Asn, Glu to Gln, and Cys to Ser . In addition, binding of ions or charged ligands may also be sensitive to the ΔΨ, inducing conformational changes as long as the time of binding exceeds the duration of the conformation transition.…”

Section: Tool Kits Of Common Sensorsmentioning

confidence: 99%

“…This type of proton-titratable residues are likely to be sensitive to point mutations to their corresponding non-titratable analogous, namely Asp to Asn, Glu to Gln, and Cys to Ser. [60][61][62][63] In addition, binding of ions or charged ligands may also be sensitive to the ΔΨ, inducing conformational changes as long as the time Figure 2. Legend on next page.…”

Section: Tool Kits Of Common Sensorsmentioning

confidence: 99%

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Interplay between the electrostatic membrane potential and conformational changes in membrane proteins

Zhang

2019

Protein Science

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Transmembrane electrostatic membrane potential is a major energy source of the cell. Importantly, it determines the structure as well as function of charge‐carrying membrane proteins. Here, we discuss the relationship between membrane potential and membrane proteins, in particular whether the conformation of these proteins is integrally connected to the membrane potential. Together, these concepts provide a framework for rationalizing the types of conformational changes that have been observed in membrane proteins and for better understanding the electrostatic effects of the membrane potential on both reversible as well as unidirectional dynamic processes of membrane proteins.

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Section: Tool Kits Of Common Sensorsmentioning

confidence: 99%

Section: Tool Kits Of Common Sensorsmentioning

confidence: 99%

Interplay between the electrostatic membrane potential and conformational changes in membrane proteins

Zhang

2019

Protein Science

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“…Specific details have been discussed in introduction. Studies on other rhodopsin [ 24 ] pointed out that the conserved Glu/Asp at the CG deprotonates during proton transfer, and the dissociated proton moves along the direction of the electric field, converting the electrostatic potential energy into the mechanical energy needed for conformational change. This conclusion enlightened that the E90 deprotonation in ChR2 may play the same role.…”

Section: Results and Discussionmentioning

confidence: 99%

The Mechanism of the Channel Opening in Channelrhodopsin-2: A Molecular Dynamics Simulation

Zhang

Yuan

2023

IJMS

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Channelrhodopsin-2 (ChR2) has been one of the most important objects in the study of optogenetics. The retinal chromophore molecule absorbs photons and undergoes an isomerization reaction, which triggers the photocycle, resulting in a series of conformational changes. In this study, a series of intermediate structures (including D470, P500, P390-early, P390-late, and P520 states) of ChR2 in the photocycle were modeled, and molecular dynamics (MD) simulations were performed to elucidate the mechanism of ion channel opening of ChR2. The maximum absorption wavelength of these intermediates calculated by time-dependent density function theory (TD-DFT) is in general agreement with the experimental values, the distribution of water density gradually increases in the process of photocycle, and the radius of the ion channel is larger than 6 Å. All these results indicate that our structural models of the intermediates are reasonable. The evolution of protonation state of E90 during the photocycle is explained. E90 will deprotonate when the P390-early transforms into P390-late, in which the two conformations of P390-early and P390-late obtained from the simulations are consistent with the experimental descriptions. To validate the conductive P520 state, the potential mean force (PMF) of Na+ ions passing through the P520 intermediate was calculated by using steered molecular dynamics (SMD) simulation combined with umbrella sampling. The result shows that the Na+ ions passing through the channel with a very low energy barrier, especially in the central gate, is almost barrierless. This indicates that the channel is open in the P520 state.

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“…To obtain energy barriers of Na + translocation through different states of β 2 AR states, we estimated a number of US and unbiased MD simulations. The highly conserved acidic residue D 2.50 is deeply buried inside the TM region, and it is protonated during the activation of some class A GPCRs. − Therefore, simulations were run on inactive β 2 AR with the key Na + -coordinating residue D79 2.50 charged and on active β 2 AR with either a charged or a neutral (protonated) D79 2.50 .…”

Section: Results and Discussionmentioning

confidence: 99%

Translocation Mechanism of Allosteric Sodium Ions in β₂-Adrenoceptor

Yuan

Chan

2022

J. Chem. Inf. Model.

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The allosteric modulation of G-protein-coupled receptors (GPCRs) by sodium ions has received significant attention as the crystal structures of several receptors show the binding of sodium ions (Na + ) at the conserved D 2.50 . Theoretical studies have shown that extracellular Na + would enter the allosteric D 2.50 via the orthosteric site. However, it remains unclear how the bound allosteric Na + would leave the GPCRs. In this study, we performed molecular dynamics (MD) simulations to illustrate the energy barriers of Na + transfer through the transmembrane helix bundle of β 2 AR. In contrast to the postulations from other GPCRs, the translocation of this allosteric Na + into the intracellular side is found to be significantly difficult. Hence, the translocation direction could be receptor-specific.

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Proton transfer during class-A GPCR activation: do the CWxP motif and the membrane potential act in concert?

Abstract: Compliance with Ethical Standards Conflict of interest Xuejun C. Zhang, Ye Zhou, and Can Cao declare that they have no conflict of interest. Human and animal rights and informed consent This article does not contain any studies with human or animal subjects performed by any of the authors.

Cited by 7 publications

References 43 publications

Interplay between the electrostatic membrane potential and conformational changes in membrane proteins

Interplay between the electrostatic membrane potential and conformational changes in membrane proteins

The Mechanism of the Channel Opening in Channelrhodopsin-2: A Molecular Dynamics Simulation

Translocation Mechanism of Allosteric Sodium Ions in β₂-Adrenoceptor

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Proton transfer during class-A GPCR activation: do the CWxP motif and the membrane potential act in concert?

Cited by 7 publications

References 43 publications

Interplay between the electrostatic membrane potential and conformational changes in membrane proteins

Interplay between the electrostatic membrane potential and conformational changes in membrane proteins

The Mechanism of the Channel Opening in Channelrhodopsin-2: A Molecular Dynamics Simulation

Translocation Mechanism of Allosteric Sodium Ions in β2-Adrenoceptor

Contact Info

Product

Resources

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Translocation Mechanism of Allosteric Sodium Ions in β₂-Adrenoceptor