4LKP

Crystal Structure of Apo Human Epidermal Fatty Acid Binding Protein (FABP5)

Summary for 4LKP

• Entry DOI: 10.2210/pdb4lkp/pdb
• Related: 4LKT
• Descriptor: Fatty acid-binding protein, epidermal, CHLORIDE ION, DIMETHYL SULFOXIDE, ... (6 entities in total)
• Functional Keywords: beta barrel, beta clam, fatty acid binding protein, fatty acids, nucleus, lipid binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q01469
• Total number of polymer chains: 1
• Total formula weight: 15763.53

Authors

Armstrong, E.H.,Ortlund, E.A. (deposition date: 2013-07-08, release date: 2014-03-26, Last modification date: 2024-10-16)

Primary citation

Armstrong, E.H.,Goswami, D.,Griffin, P.R.,Noy, N.,Ortlund, E.A.
Structural basis for ligand regulation of the fatty acid-binding protein 5, peroxisome proliferator-activated receptor beta / delta (FABP5-PPAR beta / delta ) signaling pathway.
J.Biol.Chem., 289:14941-14954, 2014

PubMed Abstract: Fatty acid-binding proteins (FABPs) are a widely expressed group of calycins that play a well established role in solubilizing cellular fatty acids. Recent studies, however, have recast FABPs as active participants in vital lipid-signaling pathways. FABP5, like its family members, displays a promiscuous ligand binding profile, capable of interacting with numerous long chain fatty acids of varying degrees of saturation. Certain "activating" fatty acids induce the protein's cytoplasmic to nuclear translocation, stimulating PPARβ/δ transactivation; however, the rules that govern this process remain unknown. Using a range of structural and biochemical techniques, we show that both linoleic and arachidonic acid elicit FABP5's translocation by permitting allosteric communication between the ligand-sensing β2 loop and a tertiary nuclear localization signal within the α-helical cap of the protein. Furthermore, we show that more saturated, nonactivating fatty acids inhibit nuclear localization signal formation by destabilizing this activation loop, thus implicating FABP5 specifically in cis-bonded, polyunsaturated fatty acid signaling.

PubMed: 24692551
DOI: 10.1074/jbc.M113.514646

Experimental method

X-RAY DIFFRACTION (1.67 Å)