4LKP: Crystal Structure of Apo Human Epidermal Fatty Acid Binding Protein (FABP5)

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 PPARbeta/delta 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 beta2 loop and a tertiary nuclear localization signal within the alpha-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.
PDB ID: 4LKPDownload
MMDB ID: 118592
PDB Deposition Date: 2013/7/8
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.67  Å
Source Organism:
Similar Structures:
Biological Unit for 4LKP: monomeric; determined by author and by software (PISA)
Molecular Components in 4LKP
Label Count Molecule
Protein (1 molecule)
Fatty Acid-binding Protein, Epidermal(Gene symbol: FABP5)
Molecule annotation
Chemicals (5 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB