Structural basis for the ligand-binding specificity of fatty acid-binding proteins (pFABP4 and pFABP5) in gentoo penguin

Here, we report the crystal structures of ligand-unbound pFABP4, linoleate-bound pFABP4 and palmitate-bound pFABP5 from the gentoo penguin (Pygoscelis papua) at 2.1, 2.2, and 2.3 Å resolutions, respectively. The pFABP4 and pFABP5 proteins comprise a canonical β-barrel structure with two short α-helices forming a cap region and fatty acid ligand binds in the hydrophobic cavity inside the β-barrel structure.

The two linoleate-bound pFABP4 and palmitate-bound pFABP5 structures shows a different ligand-binding mode and a unique ligand-binding pocket caused by several sequence differences (A76/L78, T30/M32, underlining used to indicate pFABP4 residues). Structural comparison also shows a significantly different conformation change in the β3-β4 loop region (residues 57-62) of pFABP5 as well as flipped Phe60 residue (the corresponding residue in pFABP4 is Phe58).