title: Water-mediated recognition of simple alkyl chains by heart-type fatty-acid-binding protein.
abstract: Long-chain fatty acids (FAs) with low water solubility require fatty-acid-binding proteins (FABPs) to transport them from cytoplasm to the mitochondria for energy production. However, the precise mechanism by which these proteins recognize the various lengths of simple alkyl chains of FAs with similar high affinity remains unknown. To address this question, we employed a newly developed calorimetric method for comprehensively evaluating the affinity of FAs, sub-Angstrom X-ray crystallography to accurately determine their 3D structure, and energy calculations of the coexisting water molecules using the computer program WaterMap. Our results clearly showed that the heart-type FABP (FABP3) preferentially incorporates a U-shaped FA of C10-C18 using a lipid-compatible water cluster, and excludes longer FAs using a chain-length-limiting water cluster. These mechanisms could help us gain a general understanding of how proteins recognize diverse lipids with different chain lengths.
authors.affiliation: JST-ERATO and Graduate School of Science, Osaka University, Machikaneyama, Toyonaka, Osaka 560-0043 (Japan); Project Research Centre for Fundamental Science, Osaka University, Machikaneyama, Toyonaka, Osaka 560-0043 (Japan).
authors.forename: Shigeru
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuoka
authors.forename: Mika
authors.initials: M
authors.lastname: Hirose
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lethu
authors.forename: Hikaru
authors.initials: H
authors.lastname: Ano
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hara
authors.forename: Osamu
authors.initials: O
authors.lastname: Ichihara
authors.forename: S Roy
authors.initials: SR
authors.lastname: Kimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Murakami
authors.forename: Hanako
authors.initials: H
authors.lastname: Ishida
authors.forename: Eiichi
authors.initials: E
authors.lastname: Mizohata
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Michio
authors.initials: M
authors.lastname: Murata
mesh_terms: D001665:Binding Sites; D002151:Calorimetry; D018360:Crystallography, X-Ray; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D009206:Myocardium / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D014867:Water / Q000737:chemistry / Q000378:metabolism*
chemical_list: C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D014867:Water
keywords: fatty acids; molecular dynamics; molecular evolution; structural biology; water clusters