Journal of Biological Physics

, Volume 44, Issue 3, pp 331–344 | Cite as

Exploring conformational states and helical packings in the P2X receptor transmembrane domain by molecular dynamics simulation

  • Guo-Hua LiEmail author
Original Paper


The P2X receptor is a trimeric transmembrane protein that acts as an ATP-gated ion channel. Its transmembrane domain (TMD) contains only six helices and three of them, the M2 helices, line the ion conduction pathway. Here, using molecular dynamics simulation, I identify four conformational states of the TMD that are associated with four types of packing between M2 helices. Packing in the extracellular half of the M2 helix produces closed conformations, while packing in the intracellular half produces both open and closed conformations. State transition is observed and supports a mechanism where iris-like twisting of the M2 helices switches the location of helical packing between the extracellular and the intracellular halves of the helices. In addition, this twisting motion alters the position and orientation of residue side-chains relative to the pore and therefore influences the pore geometry and possibly ion permeation. Helical packing, on the other hand, may restrict the twisting motion and generate discrete conformational states.


Helical packing P2X Ion channel Molecular dynamics Transmembrane helix 



This work was supported by a grant to G.H.L. from the National Natural Science Foundation of China (Grant No. 30972861).

Compliance with ethical standards

Conflict of interest

The author declares no conflict of interest.

Supplementary material

10867_2018_9493_MOESM1_ESM.pse (994 kb)
Supplementary File 1 An example of axial projection of the Cα atoms from a simulation of the TMD-4DW0 model in a POPC bilayer. The file is viewed using PyMol. (PSE 994 kb)
10867_2018_9493_MOESM2_ESM.pse (432 kb)
Supplementary Movie 1 Twisting of M2 helices changes the organization of the M2 bundle. The pore is initially closed in the outer portion of the structure. Twisting of M2 helices increases the outer portion, creating a continuous open pore. In addition, the relative positions of residues are changed, which is important for packing and channel gating. This movie is generated by changing the azimuth angles while the other parameters remain constant. (PSE 431 kb)
10867_2018_9493_MOESM3_ESM.pse (419 kb)
Supplementary Movie 2 Rotation of M2 helices changes the positions and orientations of the residue side-chains. This movie is generated by changing the rotation angles while the other parameters remain constant. (PSE 418 kb)
10867_2018_9493_MOESM4_ESM.png (135 kb)
Supplementary Fig. S1 An example showing the measurements of the stability of MD simulation. The top panel is a plot of RMSD of Cα atoms relative to the start conformation. The bottom panel is a plot of the PH values during the simulation. At about 30 ns, both the RMSD and PH curves reach plateaus. (PNG 134 kb)
10867_2018_9493_MOESM5_ESM.png (90 kb)
Supplementary Fig. S2 A schematic diagram showing the collective changes in residue packing due to axial rotation of the M2 helices. In type 1 packing, L339 side-chain splays outwards and interacts weakly with the downstream M2 helix. In type 2 packing, M2 helices rotate in a clockwise direction (seen from the extracellular end of the M2 helices), this brings L339 closer to the target helices, and shifts the binding sites of A344 and A347 and L348 collectively. The Supplementary Movie 2 also shows how the rotation affect the packing pattern between M2 helices. (PNG 90 kb)
10867_2018_9493_MOESM6_ESM.png (218 kb)
Supplementary Fig. S3 The position of the residue L351 in the C1 state (A), the C2 state (B), the O1 state (C) and the D1 state (D). This example is from a simulation of the TMD-4DW1 model in a POPC bilayer. (PNG 217 kb)


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© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Anesthesiology and Critical Care Medicine, Translational Neuroscience Center, West China HospitalSichuan UniversityChengduChina

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