The human fatty acid-binding protein family: Evolutionary divergences and functions

Rebecca L Smathers,Dennis R Petersen

doi:10.1186/1479-7364-5-3-170

Rebecca L Smathers, Dennis R Petersen

Open Access

https://doi.org/10.1186/1479-7364-5-3-170

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Journal: Human genomics	Publication Date: Jan 1, 2011
Citations: 361	License type: cc-by

Affiliation: University of Colorado Denver

Abstract

Fatty acid-binding proteins (FABPs) are members of the intracellular lipid-binding protein (iLBP) family and are involved in reversibly binding intracellular hydrophobic ligands and trafficking them throughout cellular compartments, including the peroxisomes, mitochondria, endoplasmic reticulum and nucleus. FABPs are small, structurally conserved cytosolic proteins consisting of a water-filled, interior-binding pocket surrounded by ten anti-parallel beta sheets, forming a beta barrel. At the superior surface, two alpha-helices cap the pocket and are thought to regulate binding. FABPs have broad specificity, including the ability to bind long-chain (C16-C20) fatty acids, eicosanoids, bile salts and peroxisome proliferators. FABPs demonstrate strong evolutionary conservation and are present in a spectrum of species including Drosophila melanogaster, Caenorhabditis elegans, mouse and human. The human genome consists of nine putatively functional protein-coding FABP genes. The most recently identified family member, FABP12, has been less studied.

Highlights

Hydrophobic ligands, such as fatty acids (FAs) and their acyl-CoA derivatives (FA-CoA), serve many biological functions within the cell
The hydrocarbon tail of bound FA is located in the cavity formed by side chains of hydrophobic amino acids, with the first segment of the FA (C-4) making van der Waals contact with Cys[117], the middle segment (C5–C14) interacting with Tyr[19] and a salt bridge formed by Asp[76] and Arg[78], and the last segment (C15–C18) protruding towards the solvent in close proximity to Val[32], Phe[57] and Lys58.110 Tyr[19] is phosphorylated by the insulin receptor kinase, which has been shown significantly to reduce both the affinity for long-chain FAs (LCFAs) and the release of ligand, demonstrating the involvement of A-fatty acid-binding proteins (FABPs) in the lipogenic pathway.[111,114,115]
This study showed that several cholate molecules can bind to hydrophobic patches on the surface of the protein, and that two to three cholate molecules can bind within the core of a single Il-FABP molecule