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

Chang Woo Lee, Jung Eun Kim, Hackwon Do, Ryeo Ok Kim, Sung Gu Lee, Hyun Ho Park, Jeong Ho Chang, Joung Han Yim, Hyun Park, Il Chan Kim, Jun Hyuck Lee

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Fatty acid-binding proteins (FABPs) are involved in transporting hydrophobic fatty acids between various aqueous compartments of the cell by directly binding ligands inside their β-barrel cavities. Here, we report the crystal structures of ligand-unbound pFABP4, linoleate-bound pFABP4, and palmitate-bound pFABP5, obtained from gentoo penguin (Pygoscelis papua), at a resolution of 2.1 Å, 2.2 Å, and 2.3 Å, respectively. The pFABP4 and pFABP5 proteins have a canonical β-barrel structure with two short α-helices that form a cap region and fatty acid ligand binding sites in the hydrophobic cavity within the β-barrel structure. Linoleate-bound pFABP4 and palmitate-bound pFABP5 possess different ligand-binding modes and a unique ligand-binding pocket due to several sequence dissimilarities (A76/L78, T30/M32, underlining indicates pFABP4 residues) between the two proteins. Structural comparison revealed significantly different conformational changes in the β3-β4 loop region (residues 57-62) as well as the flipped Phe60 residue of pFABP5 than that in pFABP4 (the corresponding residue is Phe58). A ligand-binding study using fluorophore displacement assays shows that pFABP4 has a relatively strong affinity for linoleate as compared to pFABP5. In contrast, pFABP5 exhibits higher affinity for palmitate than that for pFABP4. In conclusion, our high-resolution structures and ligand-binding studies provide useful insights into the ligand-binding preferences of pFABPs based on key protein-ligand interactions.

Original languageEnglish
Article number34299
Pages (from-to)12-18
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume465
Issue number1
DOIs
StatePublished - 20 Jul 2015

Keywords

  • Crystal structure
  • Fatty acid-binding protein
  • Gentoo penguin (Pygoscelis papua)
  • X-ray crystallography
  • β-barrel protein

Fingerprint

Dive into the research topics of 'Structural basis for the ligand-binding specificity of fatty acid-binding proteins (pFABP4 and pFABP5) in gentoo penguin'. Together they form a unique fingerprint.

Cite this