PDBsum entry 4lkt

Lipid binding protein

PDB id: 4lkt

Contents

Protein chains

137 a.a.

Ligands

EIC ×4

GOL ×9

SO4 ×3

TAR ×3

CIT

NH4 ×3

Metals

_CL

Waters ×69

PDB id:

4lkt

Name:

Lipid binding protein

Title:

Crystal structure of human epidermal fatty acid binding protein (fabp5) in complex with linoleic acid

Structure:

Fatty acid-binding protein, epidermal. Chain: a, b, c, d. Synonym: epidermal-type fatty acid-binding protein, e-fabp, fatty acid-binding protein 5, psoriasis-associated fatty acid-binding protein homolog, pa-fabp. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fabp5. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.57Å R-factor: 0.207 R-free: 0.259

Authors:

E.H.Armstrong,E.A.Ortlund

Key ref:

E.H.Armstrong et al. (2014). Structural basis for ligand regulation of the fatty acid-binding protein 5, peroxisome proliferator-activated receptor β/δ (FABP5-PPARβ/δ) signaling pathway. J Biol Chem, 289, 14941-14954. PubMed id: 24692551 DOI: 10.1074/jbc.M113.514646

Date:

08-Jul-13 Release date: 26-Mar-14

Protein chains

Q01469  (FABP5_HUMAN) -  Fatty acid-binding protein 5 from Homo sapiens

Seq: 135 a.a.

Struc: 137 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M113.514646

J Biol Chem 289:14941-14954 (2014)

PubMed id: 24692551

Structural basis for ligand regulation of the fatty acid-binding protein 5, peroxisome proliferator-activated receptor β/δ (FABP5-PPARβ/δ) signaling pathway.

E.H.Armstrong, D.Goswami, P.R.Griffin, N.Noy, E.A.Ortlund.

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.