Choi, Sun-Hye Hong, Myoung-Ki Kim, Hyeon-Joong Ryoo, Nayeon Rhim, Hyewhon Nah, Seung-Yeol Kang, Lin-Woo 2024-01-20T07:04:07Z 2024-01-20T07:04:07Z 2021-09-05 2015-05 2059-7983 https://pubs.kist.re.kr/handle/201004/125511 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 Betv1 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 Ca2+ transients in neuronal cells or activate Ca2+-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. English INT UNION CRYSTALLOGRAPHY BET V 1 CRYSTAL-STRUCTURE RECEPTOR-LIGAND XENOPUS OOCYTES X-RAY GINTONIN INVOLVEMENT ALLERGEN ACTIVATION INGREDIENT Structure of ginseng major latex-like protein 151 and its proposed lysophosphatidic acid-binding mechanism Article 10.1107/S139900471500259X 1 Acta Crystallographica Section D - Structural Biology, v.71, pp.1039 - 1050 Acta Crystallographica Section D - Structural Biology 71 1039 1050 scie scopus 000354376700002 2-s2.0-84929241627 Biochemical Research Methods Biochemistry & Molecular Biology Biophysics Crystallography Biochemistry & Molecular Biology Biophysics Crystallography Article BET V 1 CRYSTAL-STRUCTURE RECEPTOR-LIGAND XENOPUS OOCYTES X-RAY GINTONIN INVOLVEMENT ALLERGEN ACTIVATION INGREDIENT Panax ginseng ginseng major latex-like protein 151 plant LPA-binding protein G protein-coupled LPA receptor