Correlation Engine 2.0
Clear Search sequence regions

Sizes of these terms reflect their relevance to your search.

G-protein-coupled receptors (GPCR) are a family of membrane receptors that play important roles in the regulation of various physiological phenomena. LPA receptors (LPA1-6) are members of the class A GPCRs, which transduce a lysophosphatidic acid (LPA) signal across the cell membrane and evoke various responses, including cellular survival, proliferation, differentiation, and migration. The crystal structure of LPA6 revealed a gap between its transmembrane helices (TMs), which is opened toward the membrane side. This led to the proposal of the "lateral access model," in which its lipophilic ligand directly enters the binding pocket through the gap structure at the membrane. In this study, we performed molecular dynamics (MD) simulations and Markov state model (MSM) analyses of LPA6 and LPA, to elucidate the long timescale dynamics of the ligand binding process. The results from the 71.4-μs MD simulation suggested that the flexibility of the TMs constituting the gap structure enables the lateral entrance of the ligand, and the key interactions between the receptor and ligand facilitate the transition state of the ligand binding process.


Rieko Suenaga, Mizuki Takemoto, Asuka Inoue, Ryuichiro Ishitani, Osamu Nureki. Lateral access mechanism of LPA receptor probed by molecular dynamics simulation. PloS one. 2022;17(2):e0263296

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 35113924

View Full Text