Characterization of fatty acid binding and transfer from ∆98∆, a functional all-β abridged form of IFABP

• Δ98Δ binds fatty acids with lower affinity than IFABP.
• This variant shows a higher FA affinity than previous helix-less constructs.
• It shows a ‘diffusional’ fatty acid transfer mechanism.
• Δ98Δ physically interacts with artificial membranes.

Intestinal fatty acid binding protein (IFABP) is an intracellular lipid binding protein whose specific functions within the cell are still uncertain. An abbreviated version of IFABP encompassing residues 29–126, dubbed Δ98Δ is a stable product of limited proteolysis with clostripain of holo-IFABP. Cumulative evidence shows that Δ98Δ adopts a stable, monomeric and functional fold, with compact core and loose periphery. In agreement with previous results, this abridged variant indicates that the helical domain is not necessary to preserve the general topology of IFABP's β-barrel and that the helix-turn-helix motif is a fundamental element of the portal region involved in ligand binding and protein–membrane interactions. Results presented here suggest that Δ98Δ binds fatty acids with affinities lower than IFABP but higher than those shown by previous helix-less variants, shows a ‘diffusional’ fatty acid transfer mechanism and it interacts with artificial membranes. This work highlights the importance of the β-barrel of IFABP for its specific functions.