Identification of a non-classical three-dimensional nuclear localization signal in the intestinal fatty acid binding protein.

Mariana Suárez,Lucía Canclini,Adriana Esteves,Stephan N Witt

doi:10.1371/journal.pone.0242312

Abstract

The intestinal fatty acid binding protein (FABP) is a small protein expressed along the small intestine that bind long-chain fatty acids and other hydrophobic ligands. Several lines of evidence suggest that, once in the nucleus, it interacts with nuclear receptors, activating them and thus transferring the bound ligand into the nucleus. Previous work by our group suggests that FABP2 would participate in the cytoplasm-nucleus translocation of fatty acids. Because the consensus NLS is absent in the sequence of FABP2, we propose that a 3D signal could be responsible for its nuclear translocation. The results obtained by transfection assays of recombinant wild type and mutated forms of Danio rerio Fabp2 in Caco-2 cell cultures, showed that lysine 17, arginine 29 and lysine 30 residues, which are located in the helix-turn-helix region, would constitute a functional non-classical three-dimensional NLS.

Highlights

Fatty acid binding proteins (FABPs) belong to the intracellular lipid binding proteins [1]
Due to our interest in the existence of a Nuclear Localization Signal (NLS) in the Danio rerio Fabp2 protein, we analyzed the structure of the α-helical region of this protein
The Nuclear Localization Signals (NLS) described for hCRABPII, mFABP4 and hFABP5 is composed of a 3D triad of basic amino acids (KRK) [35, 37,38,39]

Summary

Introduction

Fatty acid binding proteins (FABPs) belong to the intracellular lipid binding proteins (iLPs) [1]. FABPs were described for the first time by Ockner and co-workers as intracellular cytosolic proteins with a relatively low molecular mass (14–15 kDa), able to bind fatty acids and other lipid ligands [2]. FABPs could be involved in the intracellular transport and compartmentalization of the ligands, as well as in the removal of fatty acids from intracellular depots [11,12,13]. Members of this family of proteins might exert tissue-specific functions and regulatory functions outside their tissue of expression [14, 15].

Methods

Results

Conclusion