scholarly journals FABP7 Binds to Fatty Acid Micelles: Implications for Lipid Transport

2021 ◽  
Author(s):  
Stefan Lenz ◽  
Iulia Bodnariuc ◽  
Margaret Renaud-Young ◽  
Tanille M. Shandro ◽  
Justin L. MacCallum
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Structural Data ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding ◽  
Differential Scanning Fluorimetry ◽  
Biophysical Approach ◽  
Dynamics Simulations ◽  
Cellular Compartments ◽  
Insight Into

The transport of hydrophobic molecules, including long-chain fatty acids, within cells is highly dynamic. Hydrophobic molecules are unable to freely diffuse through the aqueous cytoplasm without a transporter. Fatty acid binding proteins (FABP) transport these molecules to different cellular compartments. As part of their transport, FABPs often associate with cell membranes to acquire and deliver their bound cargo. Understanding the nature of this transport is becoming increasingly important because lipid signaling functions are associated with metabolic pathways impacting disease pathologies such as carcinomas, autism and schizophrenia. Herein, we focus on Brain fatty acid binding protein (FABP7), which demonstrates localization to the cytoplasm and nucleus, influencing transcription and fatty acid metabolism. We use a combined biophysical approach to elucidate the interaction between FABP7 and model membranes. Specifically, we use microscale thermophoresis to show that FABP7 can bind oleic acid (OA) and docosahexaenoic acid (DHA) micelles, while differential scanning fluorimetry experiments show binding lowers the melting temperature of FABP7. Structural data from NMR and multiscale molecular dynamics simulations reveals that the interaction between FABP7 and micelles is through FABP7 portal region residues. Our simulations also capture binding events where fatty acids dissociate from the model membrane and bind to FABP7. Overall, our data reveals a novel interaction between FABP7 and OA or DHA micelles and provides key structural insight into the transport of hydrophobic molecules.

scholarly journals A novel acyl-CoA-binding protein from bovine liver. Effect on fatty acid synthesis

1987 ◽  
Vol 241 (1) ◽  
pp. 189-192 ◽  
Author(s):  
I B Mogensen ◽  
H Schulenberg ◽  
H O Hansen ◽  
F Spener ◽  
J Knudsen
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Binding Protein ◽  
Fatty Acid Synthetase ◽  
Bovine Liver ◽  
Acid Synthesis ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding ◽  
Medium Chain ◽  
Chain Acyl

Bovine liver was shown to contain a hitherto undescribed medium-chain acyl-CoA-binding protein. The protein co-purifies with fatty-acid-binding proteins, but was, unlike these proteins, unable to bind fatty acids. The protein induced synthesis of medium-chain acyl-CoA esters on incubation with goat mammary-gland fatty acid synthetase. The possible function of the protein is discussed.

scholarly journals Interaction of fatty acids with recombinant rat intestinal and liver fatty acid-binding proteins

1991 ◽  
Vol 286 (1) ◽  
pp. 300-309 ◽  
Author(s):  
Gyorgy Nemecz ◽  
Timothy Hubbell ◽  
John R. Jefferson ◽  
John B. Lowe ◽  
Friedhelm Schroeder
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Binding Proteins ◽  
Fatty Acid Binding Proteins ◽  
Liver Fatty Acid ◽  
Fatty Acid Binding

scholarly journals Fatty acid binding proteins have the potential to channel dietary fatty acids into enterocyte nuclei

2015 ◽  
Vol 57 (2) ◽  
pp. 219-232 ◽  
Author(s):  
Adriana Esteves ◽  
Anja Knoll-Gellida ◽  
Lucia Canclini ◽  
Maria Cecilia Silvarrey ◽  
Michèle André ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Binding Proteins ◽  
Dietary Fatty Acids ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding

scholarly journals Omega-3 fatty acids transport through the placenta

2016 ◽  
Vol 2 (1) ◽  
pp. 1-8
Author(s):  
Ariful Islam ◽  
Takanori Kodama ◽  
Yui Yamamoto ◽  
Majid Ebrahimi ◽  
Hirofumi Miyazaki ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Placental Transfer ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Transport ◽  
Omega 3 ◽  
Fatty Acid Binding ◽  
Membrane Bound ◽  
Fatty Acid Transport Proteins

The placenta is a temporary vital organ for sustaining the development of the fetus throughout gestation. Although the fatty acid composition delivered to the fetus is largely determined by maternal circulating levels, the placenta preferentially transfers physiologically important long-chain polyunsaturated fatty acids (LC-PUFAs), particularly omega-3 (n-3) FAs. The precise mechanisms governing these transfers were covered in a veil, but have started to be revealed gradually. Several evidences suggest fatty acid transport proteins (FATPs), placental specific membrane bound fatty acid binding proteins (pFABPpm) and fatty acid translocases (FAT/CD36) involved in LC-PUFAs uptake. Our studies have shown that the placental transfer of omega-3 FAs through the trophoblast cells is largely contributed by fatty acid binding protein 3 (FABP3). Recently there are considerable interests in the potential for dietary omega-3 FAs as a therapeutic intervention for fetal disorders. In fact, prenatal supply of omega-3 FAs is essential for brain and retinal development. Recent findings suggest a potential opportunity of omega-3 FA interventions to decrease the incidence of type 2 diabetes in future generations. In this review, we discuss the molecular mechanism of transportation of omega-3 FAs through the placenta and how omega-3 FAs deficiency/supplementation impact on fetal development.Asian J. Med. Biol. Res. March 2016, 2(1): 1-8

Enterocyte fatty acid uptake and intestinal fatty acid-binding protein

2004 ◽  
Vol 32 (1) ◽  
pp. 75-78 ◽  
Author(s):  
P. Tso ◽  
A. Nauli ◽  
C.-M. Lo
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Brush Border Membrane ◽  
Fatty Acid Uptake ◽  
Current Understanding ◽  
Fatty Acid Binding Proteins ◽  
Acid Uptake ◽  
Micellar Solubilization ◽  
Fatty Acid Binding

This article reviews our current understanding of the uptake of fatty acids by the enterocytes of the intestine. The micellar solubilization of fatty acids by bile salts and the factors regulating that process are discussed. The mechanism of how micellar solubilization of fatty acids promotes the uptake of fatty acids by enterocytes and their relative importance is reviewed. Additionally, discussion of the various fatty acid transporters located at the brush border membrane of the enterocytes is included. Finally, a summary of our current understanding of the function of fatty-acid-binding proteins inside enterocytes is provided.

Fatty acid binding sites of rodent adipocyte and heart fatty acid binding proteins: characterization using fluorescent fatty acids

Biochemistry ◽  
1990 ◽  
Vol 29 (40) ◽  
pp. 9305-9311 ◽  
Author(s):  
Margo G. Wootan ◽  
Nathan M. Bass ◽  
David A. Bernlohr ◽  
Judith Storch
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Binding Sites ◽  
Binding Proteins ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding

scholarly journals Brain fatty acid binding protein exhibits non-preferential and mutation-resistant binding towards fatty acids

2021 ◽  
Author(s):  
Iulia Bodnariuc ◽  
Stefan Lenz ◽  
Margaret Renaud-Young ◽  
Tanille Shandro ◽  
Hiroaki Ishida ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Molecular Dynamics Simulations ◽  
Nuclear Localization ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Dynamics Simulations

Members of the fatty acid binding protein (FABP) family function as intracellular transporters of long chain fatty acids and other hydrophobic molecules to different cellular compartments. Brain fatty acid binding protein (FABP7) exhibits ligand-directed differences in cellular transport behavior. For example, when FABP7 binds to docosahexaenoic acid (DHA), the complex relocates to the nucleus and influences transcriptional activity, whereas FABP7 bound with monosaturated fatty acids remain in the cytosol. We used a variety of biophysical techniques to enhance understanding of ligand-directed transport. Specifically, we examine how FABP7 binds to fatty acids, including saturated stearic acid (SA), monounsaturated oleic acid (OA), and polyunsaturated DHA. We find that at 37°C FABP7 has near equivalent binding affinities for the fatty acids, while at lower temperatures, FABP7 exhibits a preference for the unsaturated fatty acids. Therefore, nuclear localization of the FABP7-DHA complex cannot be explained by binding preferences. Using NMR spectroscopy and molecular dynamics simulations, we observe that DHA uniquely affects the portal region of FABP7, which could enhance the complex's nuclear localization. Mutations to purported critical binding residues (R126L and Y128F) have little effect on fatty acid binding, with molecular dynamics simulations revealing that the bound fatty acid can adopt binding poses that can accommodate the mutations.

scholarly journals PickPocket : Pocket binding prediction for specific ligands family using neural networks.

2020 ◽  
Author(s):  
Benjamin Thomas VIART ◽  
Claudio Lorenzi ◽  
María Moriel-Carretero ◽  
Sofia Kossida
Keyword(s):  
Neural Networks ◽  
Fatty Acid ◽  
Ligand Binding ◽  
Binding Sites ◽  
Structural Data ◽  
Binding Pocket ◽  
Fatty Acid Binding Proteins ◽  
Binding Prediction ◽  
Fatty Acid Binding ◽  
Binding Pockets

Most of the protein biological functions occur through contacts with other proteins or ligands. The residues that constitute the contact surface of a ligand-binding pocket are usually located far away within its sequence. Therefore, the identification of such motifs is more challenging than the linear protein domains. To discover new binding sites, we developed a tool called PickPocket that focuses on a small set of user-defined ligands and uses neural networks to train a ligand-binding prediction model. We tested PickPocket on fatty acid-like ligands due to their structural similarities and their under-representation in the ligand-pocket binding literature. Our results show that for fatty acid-like molecules, pocket descriptors and secondary structures are enough to obtain predictions with accuracy >90% using a dataset of 1740 manually curated ligand-binding pockets. The trained model could also successfully predict the ligand-binding pockets using unseen structural data of two recently reported fatty acid-binding proteins. We think that the PickPocket tool can help to discover new protein functions by investigating the binding sites of specific ligand families. The source code and all datasets contained in this work are freely available at https://github.com/benjaminviart/PickPocket .

Molecular mechanism with regard to the binding selectivity of inhibitors toward FABP5 and FABP7 explored by multiple short molecular dynamics simulations and free energy analyses

2020 ◽  
Vol 22 (4) ◽  
pp. 2262-2275 ◽  
Author(s):  
Jianzhong Chen ◽  
Xinguo Liu ◽  
Shaolong Zhang ◽  
Junxiao Chen ◽  
Haibo Sun ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Fatty Acid ◽  
Molecular Dynamics Simulations ◽  
Molecular Mechanism ◽  
Binding Proteins ◽  
Fatty Acid Binding Proteins ◽  
Binding Selectivity ◽  
Fatty Acid Binding ◽  
Dynamics Simulations

Recently, fatty acid binding proteins 5 and 7 (FABP5 and FABP7) have been regarded as the prospective targets for clinically treating multiple diseases related to FABPs.

scholarly journals Different functions of intestinal and liver-type fatty acid-binding proteins in intestine and in whole body energy homeostasis

2011 ◽  
Vol 300 (5) ◽  
pp. G803-G814 ◽  
Author(s):  
William Stacy Lagakos ◽  
Angela Marie Gajda ◽  
Luis Agellon ◽  
Bert Binas ◽  
Victor Choi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Null Models ◽  
Dietary Fatty Acids ◽  
Fat Free Mass ◽  
Whole Body ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding ◽  
Triacylglycerol Synthesis

It has long been known that mammalian enterocytes coexpress two members of the fatty acid-binding protein (FABP) family, the intestinal FABP (IFABP) and the liver FABP (LFABP). Both bind long-chain fatty acids and have similar though not identical distributions in the intestinal tract. While a number of in vitro properties suggest the potential for different functions, the underlying reasons for expression of both proteins in the same cells are not known. Utilizing mice genetically lacking either IFABP or LFABP, we directly demonstrate that each of the enterocyte FABPs participates in specific pathways of intestinal lipid metabolism. In particular, LFABP appears to target fatty acids toward oxidative pathways and dietary monoacylglycerols toward anabolic pathways, while IFABP targets dietary fatty acids toward triacylglycerol synthesis. The two FABP-null models also displayed differences in whole body response to fasting, with LFABP-null animals losing less fat-free mass and IFABP-null animals losing more fat mass relative to wild-type mice. The metabolic changes observed in both null models appear to occur by nontranscriptional mechanisms, supporting the hypothesis that the enterocyte FABPs are specifically trafficking their ligands to their respective metabolic fates.

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