Structure of ginseng major latex-like protein 151 and its proposed lysophosphatidic acid-binding mechanism

Abstract

Lysophosphatidic acid (LPA) is a phospholipid growth factor with myriad effects on biological systems. LPA is usually present bound to animal plasma proteins such as albumin or gelsolin. When LPA complexes with plasma proteins, it binds to its cognate receptors with higher affinity than when it is free. Recently, gintonin from ginseng was found to bind to LPA and to activate mammalian LPA receptors. Gintonin contains two components: ginseng major latex-like protein 151 (GLP) and ginseng ribonuclease-like storage protein. Here, the crystal structure of GLP is reported, which belongs to the plant Bet v 1 superfamily, and a model is proposed for how GLP binds LPA. Amino-acid residues of GLP recognizing LPA were identified using site-directed mutagenesis and isothermal titration calorimetry. The resulting GLP mutants were used to study the activation of LPA receptor-dependent signalling pathways. In contrast to wild-type GLP, the H147A mutant did not bind LPA, elicit intracellular Ca(2+) transients in neuronal cells or activate Ca(2+)-dependent Cl(-) channels in Xenopus oocytes. Based on these results, a mechanism by which GLP recognizes LPA and its requirement to activate G protein-coupled LPA receptors to elicit diverse biological responses were proposed.

Gintonin stimulates gliotransmitter release in cortical primary astrocytes

“…showed GLP151 protein could function as a carrier/transporter of LPA and deliver it to LPA receptors [20]. The present study provides additional information showing that gintonin might be a main regulator of ginseng-induced gliotransmitter release by acting on astrocytes.…”

“…The recent elucidation of the three-dimensional structure of GLP151, a protein component of gintonin, revealed how it binds to LPA. The phosphate head group of LPA binds to imidazole ring histidine residues at the C-terminal of GLP151 with hydrogen bonds and acyl-chains of LPA bind to another portion of GLP151 [20]. In addition, they Time course of gintonin-mediated glutamate release.…”

Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer’s Disease

“…Recent study showed how GLP151 protein as a protein component of gintonin binds to LPA through the elucidation of three-dimensional structure of GLP151. The phosphate group of LPA binds to the imidazole ring of histidine residues at C-terminal of GLP151 with hydrogen bonds and acyl-chain of LPA interacts with other amino acids though hydrophobic interactions of GLP151 ( Choi et al, 2015b ). GLP151 protein was identified as a first plant-derived carrier or transporter of LPA, and deliver LPA to cognitive LPA receptors ( Choi et al, 2015b ).…”

Structure ofAlliumlachrymatory factor synthase elucidates catalysis on sulfenic acid substrate

“…Pyrabactin-resistant protein-like proteins (PYLs) [maximal score for Arabidopsis thaliana PYL10 (31)] are intracellular receptors for a plant hormone, abscisic acid (ABA). Ginseng major latex-like protein 151 (MLP151), which is thought to be associated with lysophosphatidic acid regulation, is a member of the PR-10/Bet v 1-type plant allergens (32, 33). ZhuI of Streptomyces sp.…”