Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Li GH

PROVIDER: S-EPMC6082803 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Li Guo-Hua GH

Journal of biological physics 20180402 3

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 pro ...[more]

PMID: 29611030

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Project description:Major histocompatibility complex class I proteins play a key role in the recognition and presentation of peptide antigens to the host immune system. The structure of various major histocompatibility complex class I proteins has been determined experimentally in complex with several antigenic peptides. However, the structure in the unbound (empty) form is not known. To study the conformational dynamics of the empty major histocompatibility complex class I molecule comparative molecular dynamics simulations have been performed starting from the crystal structure of a peptide bound class I peptide-binding domain in the presence and absence of a peptide ligand. Simulations including the bound peptide stayed close to the experimental start structure at both simulation temperatures (300 and 355 K) during the entire simulation of 26 ns. Several independent simulations in the absence of peptide indicate that the empty domain may not adopt a single defined conformation but is conformationally significantly more heterogeneous in particular within the alpha-helices that flank the peptide binding cleft. The calculated conformational dynamics along the protein chain correlate well with available spectroscopic data and with the observed site-specific sensitivity of the empty class I protein to proteolytic digestion. During the simulations at 300 K the binding region for the peptide N-terminus stayed close to the conformation in the bound state, whereas the anchor region for the C-terminus showed significantly larger conformational fluctuations. This included a segment at the beginning of the second alpha-helix in the domain that is likely to be involved in the interaction with the chaperone protein tapasin during the peptide-loading process. The simulation studies further indicate that peptide binding at the C- and N-terminus may follow different mechanisms that involve different degrees of induced conformational changes in the peptide-binding domain. In particular binding of the peptide C-terminus may require conformational stabilization by chaperone proteins during peptide loading.

Dataset Information

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

Publications

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

Similar Datasets

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