Solution structure and backbone dynamics of human liver fatty acid binding protein: fatty acid binding revisited.
Liver fatty acid binding protein (L-FABP), a cytosolic protein most abundant in liver, is associated with intracellular transport of fatty acids, nuclear signaling, and regulation of intracellular lipolysis. Among the members of the intracellular lipid binding protein family, L-FABP is of particular interest as it can i), bind two fatty acid molecules simultaneously and ii), accommodate a variety of bulkier physiological ligands such as bilirubin and fatty acyl CoA. To better understand the promiscuous binding and transport properties of L-FABP, we investigated structure and dynamics of human L-FABP with and without bound ligands by means of heteronuclear NMR. The overall conformation of human L-FABP shows the typical β-clam motif. Binding of two oleic acid (OA) molecules does not alter the protein conformation substantially, but perturbs the chemical shift of certain backbone and side-chain protons that are involved in OA binding according to the structure of the human L-FABP/OA complex. Comparison of the human apo and holo L-FABP structures revealed no evidence for an "open-cap" conformation or a "swivel-back" mechanism of the K90 side chain upon ligand binding, as proposed for rat L-FABP. Instead, we postulate that the lipid binding process in L-FABP is associated with backbone dynamics.
Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts, USA.
Jun
J
Cai
Christian
C
Lücke
Zhongjing
Z
Chen
Ye
Y
Qiao
Elena
E
Klimtchuk
James A
JA
Hamilton
D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D019301:Oleic Acid / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D051381:Rats; D015203:Reproducibility of Results; D012996:Solutions
D001059:Apoproteins; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D008024:Ligands; D012996:Solutions; D019301:Oleic Acid