title: Detecting structural similarity of ligand interactions in the lipid metabolic system including enzymes, lipid-binding proteins and nuclear receptors.
abstract: Nuclear receptors, intracellular lipid-binding proteins and metabolic enzymes are responsible for optimal metabolic homeostasis in higher organisms. Recent studies revealed the specific cooperation/competition among the subfamilies of these proteins. In this study, the nuclear receptor-lipid-binding protein-enzyme system, in which the interactions are mostly mediated by ligand molecules, was examined in terms of their ligand-binding structures to detect the similarity of interactions between functionally related subfamilies. The complex structures were dissected into single amino acid motifs for ligand fragment binding, and the presence and evolutionary origin of the motifs were compared among the protein families. As a result, functionally related nuclear receptor and enzyme pairs were found to share more motifs than expected, in agreement with the fact that the two families compete for the same ligand, and thus our study implies the possible co-evolution of the indirectly interacting protein system.
authors.affiliation: Open Laboratories of Advanced Bioscience and Biotechnology, Institute for Protein Research, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan.
authors.forename: Clara
authors.initials: C
authors.lastname: Shionyu-Mitsuyama
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Waku
authors.forename: Takuma
authors.initials: T
authors.lastname: Shiraki
authors.forename: Takuji
authors.initials: T
authors.lastname: Oyama
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shirai
authors.forename: Kosuke
authors.initials: K
authors.lastname: Morikawa
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000737:chemistry* / Q000145:classification; D020816:Amino Acid Motifs; D002352:Carrier Proteins / Q000737:chemistry* / Q000145:classification; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry* / Q000145:classification; D008024:Ligands; D050356:Lipid Metabolism; D010802:Phylogeny; D011487:Protein Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000145:classification; D014157:Transcription Factors / Q000737:chemistry* / Q000145:classification
chemical_list: D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D042964:Acyl-CoA Dehydrogenase