Showing papers on "Fatty acid-binding protein published in 2007"
TL;DR: Genes involved in fatty acid partitioning and binding, lipolysis, and monocyte/macrophage recruitment and inflammation are overexpressed in the human fatty liver.
Abstract: OBJECTIVE —The objective of this study is to quantitate expression of genes possibly contributing to insulin resistance and fat deposition in the human liver.
RESEARCH DESIGN AND METHODS —A total of 24 subjects who had varying amounts of histologically determined fat in the liver ranging from normal ( n = 8) to steatosis due to a nonalcoholic fatty liver (NAFL) ( n = 16) were studied. The mRNA concentrations of 21 candidate genes associated with fatty acid metabolism, inflammation, and insulin sensitivity were quantitated in liver biopsies using real-time PCR. In addition, the subjects were characterized with respect to body composition and circulating markers of insulin sensitivity.
RESULTS —The following genes were significantly upregulated in NAFL: peroxisome proliferator–activated receptor (PPAR)γ2 (2.8-fold), the monocyte-attracting chemokine CCL2 (monocyte chemoattractant protein \[MCP]-1, 1.8-fold), and four genes associated with fatty acid metabolism (acyl-CoA synthetase long-chain family member 4 [ACSL4\] \[2.8-fold\], fatty acid binding protein \[FABP]4 [3.9-fold], FABP5 [2.5-fold], and lipoprotein lipase [LPL\] \[3.6-fold\]). PPARγ coactivator 1 (PGC1) was significantly lower in subjects with NAFL than in those without. Genes significantly associated with obesity included nine genes: plasminogen activator inhibitor 1, PPARγ, PPARδ, MCP-1, CCL3 (macrophage inflammatory protein [MIP]-1α), PPARγ2, carnitine palmitoyltransferase (CPT1A), FABP4, and FABP5. The following parameters were associated with liver fat independent of obesity: serum adiponectin, insulin, C-peptide, and HDL cholesterol concentrations and the mRNA concentrations of MCP-1, MIP-1α, ACSL4, FABP4, FABP5, and LPL.
CONCLUSIONS —Genes involved in fatty acid partitioning and binding, lipolysis, and monocyte/macrophage recruitment and inflammation are overexpressed in the human fatty liver.
313 citations
TL;DR: Data show that increased urinary L-FABP after ischemia-reperfusion injury may find future use as a biomarker of acute ischemic injury.
Abstract: Fatty acid-binding proteins (FABPs) bind unsaturated fatty acids and lipid peroxidation products during tissue injury from hypoxia. We evaluated the potential role of L-type FABP (L-FABP) as a biomarker of renal ischemia in both human kidney transplant patients and animal models. Urinary L-FABP levels were measured in the first urine produced from 12 living-related kidney transplant patients immediately after reperfusion of their transplanted organs, and intravital video analysis of peritubular capillary blood flow was performed simultaneously. A significant direct correlation was found between urinary L-FABP level and both peritubular capillary blood flow and the ischemic time of the transplanted kidney (both P < 0.0001), as well as hospital stay (P < 0.05). In human-L-FABP transgenic mice subjected to ischemia-reperfusion injury, immunohistological analyses demonstrated the transition of L-FABP from the cytoplasm of proximal tubular cells to the tubular lumen. In addition, after injury, these transgenic mice demonstrated lower blood urea nitrogen levels and less histological injury than injured wild-type mice, likely due to a reduction of tissue hypoxia. In vitro experiments using a stable cell line of mouse proximal tubule cells transfected with h-L-FABP cDNA showed reduction of oxidative stress during hypoxia compared to untransfected cells. Taken together, these data show that increased urinary L-FABP after ischemic-reperfusion injury may find future use as a biomarker of acute ischemic injury.
311 citations
TL;DR: Novel hypotheses relating to NFkappaB, albumin-related protein, pentraxin, hypoferremia and the complement cascade are suggested as a basis for natural variation in susceptibility to infectious diseases.
149 citations
TL;DR: Changes in gene expression are consistent with the proposed hypocholesterolemic effect of curcumin, and an activation of a retinoic acid response element reporter employing secreted alkaline phosphatase was observed.
Abstract: Curcuminoids, the yellow pigments of curcuma, exhibit anticarcinogenic, antioxidative and hypocholesterolemic activities. To understand the molecular basis for the hypocholesterolemic effects, we examined the effects of curcumin on hepatic gene expression, using the human hepatoma cell line HepG2 as a model system. Curcumin treatment caused an up to sevenfold, concentration-dependent increase in LDL-receptor mRNA, whereas mRNAs of the genes encoding the sterol biosynthetic enzymes HMG CoA reductase and farnesyl diphosphate synthase were only slightly increased at high curcumin concentrations where cell viability was reduced. Expression of the regulatory SREBP genes was moderately increased, whereas mRNAs of the PPARα target genes CD36/fatty acid translocase and fatty acid binding protein 1 were down-regulated. LXRα expression and accumulation of mRNA of the LXRα target gene ABCg1 were increased at low curcumin concentrations. Although curcumin strongly inhibited alkaline phosphatase activity, an activation of a retinoic acid response element reporter employing secreted alkaline phosphatase was observed. These changes in gene expression are consistent with the proposed hypocholesterolemic effect of curcumin.
131 citations
TL;DR: CD36 is almost entirely responsible for AMPK-mediated stimulation of LCFA uptake in cardiomyocytes, indicating a pivotal role for CD36 in mediating changes in cardiac LCFA fluxes.
129 citations
TL;DR: The first disclosure of biphenyl azoles that are nanomolar binders of adipocyte fatty acid binding protein (aFABP or aP2) with up to thousand-fold selectivity against muscle fatty acids binding protein and epidermal fatty acidbinding protein is reported.
128 citations
TL;DR: It is thus now becoming clear that steatosis is not only a mere consequence of metabolic imbalance, but that it is also a result of discrete alterations in the beta-oxidation, transport mechanisms, and signaling pathways involved in the synthesis, systemic traffic modalities, and cellular effects of fatty acids.
Abstract: As a key metabolic organ, the liver is central to the imbalance of high-caloric diets, and particularly dietary fat consumption, in the industrialized countries and their association with the increasing prevalence of morbid obesity. By interacting with the intestinal tract and adipose tissue, the liver plays a key role in various aspects of lipid metabolism. Increasing activation of transcription factors, such as carbohydrate responsive element binding protein (ChREBP), sterol response element binding protein-1c (SREBP-1c), or forkhead box 01 (Fox01), may contribute to fatty acid synthesis. Their translocation occurs via fatty acid transporters such as fatty acid transport proteins (FATP), fatty acid translocase (FAT/CD36), caveolin-1 and fatty acid binding protein (FABP) . Eventually, the accumulation of fat in the form of lipid droplets within the hepatocytes results in hepatic steatosis which, indeed, is a hallmark of liver diseases such as non-alcoholic fatty liver disease, alcoholic fatty liver, acute fatty liver in pregnancy, and hepatitis C. In contrast, lipid accumulation within hepatocytes during liver regeneration is essential. It is thus now becoming clear that steatosis is not only a mere consequence of metabolic imbalance, but that it is also a result of discrete alterations in the beta-oxidation, transport mechanisms, and signaling pathways involved in the synthesis, systemic traffic modalities, and cellular effects of fatty acids. Such a novel insight offers potential options for improved treatment.
126 citations
TL;DR: Hypoxia enhances the expression of FABP1, -3, and -4 in term human trophoblasts, suggesting that FABPs support fat accumulation in the hypoxic placenta.
106 citations
TL;DR: In this paper, the translocation of the fatty acid transporter FAT/CD36 and plasma membrane-associated fatty acid binding protein (FABPpm) in obese rat muscle was examined, in muscle of lean and obese Zucker rats.
Abstract: We examined, in muscle of lean and obese Zucker rats, basal, insulin-induced, and contraction-induced fatty acid transporter translocation and fatty acid uptake, esterification, and oxidation. In lean rats, insulin and contraction induced the translocation of the fatty acid transporter FAT/CD36 (43 and 41%, respectively) and plasma membrane-associated fatty acid binding protein (FABPpm; 19 and 60%) and increased fatty acid uptake (63 and 40%, respectively). Insulin and contraction increased lean muscle palmitate esterification and oxidation 72 and 61%, respectively. In obese rat muscle, basal levels of sarcolemmal FAT/CD36 (+33%) and FABPpm (+14%) and fatty acid uptake (+30%) and esterification (+32%) were increased, whereas fatty acid oxidation was reduced (-28%). Insulin stimulation of obese rat muscle increased plasmalemmal FABPpm (+15%) but not plasmalemmal FAT/CD36, blunted fatty acid uptake and esterification, and failed to reduce fatty acid oxidation. In contracting obese rat muscle, the increases in fatty acid uptake and esterification and FABPpm translocation were normal, but FAT/CD36 translocation was impaired and fatty acid oxidation was blunted. There was no relationship between plasmalemmal fatty acid transporters and palmitate partitioning. In conclusion, fatty acid metabolism is impaired at several levels in muscles of obese Zucker rats; specifically, they are 1) insulin resistant with respect to FAT/CD36 translocation and fatty acid uptake, esterification, and oxidation and 2) contraction resistant with respect to fatty acid oxidation and FAT/CD36 translocation, but, conversely, 3) obese muscles are neither insulin nor contraction resistant at the level of FABPpm. Finally, 4) there is no evidence that plasmalemmal fatty acid transporters contribute to the channeling of fatty acids to specific metabolic destinations within the muscle.
80 citations
TL;DR: FABPpm has two distinct functions depending on its subcellular location: (a) it contributes to increasing sarcolemmalLCFA transport while not contributing directly to LCFA transport into mitochondria; and (b) its primary role at the mitochondria level is to transport reducing equivalents into the matrix.
Abstract: The transport of long-chain fatty acids (LCFAs) across mitochondrial membranes is regulated by carnitine palmitoyltransferase I (CPTI) activity. However, it appears that additional fatty acid transport proteins, such as fatty acid translocase (FAT)/CD36, influence not only LCFA transport across the plasma membrane, but also LCFA transport into mitochondria. Plasma membrane-associated fatty acid binding protein (FABPpm) is also known to be involved in sacrolemmal LCFA transport, and it is also present on the mitochondria. At this location, it has been identified as mitochondrial aspartate amino transferase (mAspAT), despite being structurally identical to FABPpm. Whether this protein is also involved in mitochondrial LCFA transport and oxidation remains unknown. Therefore, we have examined the ability of FABPpm/mAspAT to alter mitochondrial fatty acid oxidation. Muscle contraction increased (P 0.05). However, electrotransfection increased mAspAT activity by +70% (P < 0.05), and the mitochondrial FABPpm/mAspAT protein content was significantly correlated with mAspAT activity (r= 0.75). It is concluded that FABPpm has two distinct functions depending on its subcellular location: (a) it contributes to increasing sarcolemmal LCFA transport while not contributing directly to LCFA transport into mitochondria; and (b) its primary role at the mitochondria level is to transport reducing equivalents into the matrix.
76 citations
TL;DR: It is shown that BODIPY FL C16 binds to purified liver and intestinal fatty acid-binding proteins with high affinity at a site similar to that for the physiological fatty acid oleic acid.
Abstract: The BODIPY-labeled fatty acid analogues are a useful addition to the tools employed to study the cellular uptake and metabolism of lipids. In this study, we show that BODIPY FL C16 binds to purified liver and intestinal fatty acid-binding proteins with high affinity at a site similar to that for the physiological fatty acid oleic acid. Further, in human intestinal Caco-2 cells BODIPY FL C16 co-localizes extensively with mitochondria, endoplasmic reticulum/Golgi, and L-FABP. Virtually no esterification of BODIPY FL C16 was observed under the experimental conditions employed. We conclude that BODIPY FL C16 may be a useful tool for studying the distribution and function of FABPs in a cellular environment.
TL;DR: It is revealed that metabolic-inflammatory pathway cross-regulation by FABPs contributes to adaptive immune responses and subsequent autoimmune inflammation.
Abstract: Fatty acid-binding proteins (FABPs) act as intracellular receptors for a variety of hydrophobic compounds, enabling their diffusion within the cytoplasmic compartment. Recent studies have demonstrated the ability of FABPs to simultaneously regulate metabolic and inflammatory pathways. We investigated the role of adipocyte FABP and epithelial FABP in the development of experimental autoimmune encephalomyelitis to test the hypothesis that these FABPs impact adaptive immune responses and contribute to the pathogenesis of autoimmune disease. FABP-deficient mice exhibited a lower incidence of disease, reduced clinical symptoms of experimental autoimmune encephalomyelitis and dramatically lower levels of proinflammatory cytokine mRNA expression in CNS tissue as compared with wild-type mice. In vitro Ag recall responses of myelin oligodendrocyte glycoprotein 35-55-immunized FABP(-/-) mice showed reduced proliferation and impaired IFN-gamma production. Dendritic cells deficient for FABPs were found to be poor producers of proinflammatory cytokines and Ag presentation by FABP(-/-) dendritic cells did not promote proinflammatory T cell responses. This study reveals that metabolic-inflammatory pathway cross-regulation by FABPs contributes to adaptive immune responses and subsequent autoimmune inflammation.
TL;DR: A discrepancy was observed between age-related changes in A-FABP content in isolated adipocytes and cell diameter or lipid content variations in tissues during growth.
Abstract: Adipocyte- (A) and heart- (H) type fatty acid binding proteins (FABP) contribute to efficient fat storage and utilization, respectively. To understand regional-differences in lipid metabolism between tissues, A- and H-FABP transcript and protein levels were studied in adipocytes isolated from subcutaneous adipose tissue or skeletal muscle in growing pigs (Sus scrofa). Interestingly, H-FABP was expressed in adipocytes isolated from both sites. We also showed that A-FABP and H-FABP were expressed at a lower level in intramuscular adipocytes than in subcutaneous adipocytes. A discrepancy was observed between age-related changes in A-FABP content in isolated adipocytes and cell diameter or lipid content variations in tissues during growth.
TL;DR: The expression and antioxidative function of liver fatty acid binding protein was investigated using the bile-duct ligated model of cholestasis to find that it likely has important antioxidant function during hepatocellular oxidative stress.
TL;DR: The Ala/Ala(94)-mutation contributed significantly to reduced glycogenolysis and less severe hyperglycemia in lipid-exposed humans and was further associated with reduced body weight in a large cohort.
Abstract: Liver fatty acid-binding protein (L-FABP) is a highly conserved key factor in lipid metabolism. Amino acid replacements in L-FABP might alter its function and thereby affect glucose metabolism in l...
TL;DR: The recent studies established H- and L-FABP as major determinants of regional LCFA utilization; therefore the H−/− and L −/− mice are attractive models for studying principles of fuel selection and metabolic homeostasis.
Abstract: In vitro experiments and expression patterns have long suggested important roles for the genetically related cytosolic fatty acid binding proteins (FABPs) in lipid metabolism. However, evidence for such roles in vivo has become available only recently from genetic manipulation of FABP expression in mice. Here, we summarize the fuel-metabolic phenotypes of mice lacking the genes encoding heart-type FABP (H-/- mice) or liver-type FABP (L-/- mice). Cytosolic extracts from H-/- heart and skeletal muscle and from L-/- liver showed massively reduced binding of long chain fatty acids (LCFA) and, in case of L-/- liver, also of LCFA-CoA. Uptake, oxidation, and esterification LCFA, when measured in vivo and/or ex vivo, were markedly reduced in H-/- heart and muscle and in L-/- liver. The reduced LCFA oxidation in H-/- heart and L-/- liver was not due to reduced activity of PPARa, a fatty acid-sensitive transcription factor that determines the lipid-oxidative capacity in these organs. In H-/- mice, mechanisms of compensation were partially studied and included a redistribution of muscle mitochondria as well as increases of cardiac and skeletal muscle glucose uptakes and of hepatic ketogenesis. In skeletal muscle, the altered glucose uptake included decreased basal but increased insulin-dependent components. Metabolic compensation was only partial, however, since the H-/- mice showed decreased exercise tolerance. In conclusion, the recent studies established H- and L-FABP as major determinants of regional LCFA utilization; therefore the H-/- and L-/- mice are attractive models for studying principles of fuel selection and metabolic homeostasis.
TL;DR: Two lipogenic genes encoding diacylglycerol acyltransferase‐2 (DGAT2) and fatty acid‐binding protein‐4 (FABP4, aP2) were induced in ELOVL2‐overexpressing cells, whereas no such effect was seen on the fatty acid synthase (FAS) gene.
TL;DR: The mechanism behind intracellular fatty acid transport and subsequent nuclear receptor activation is an emerging concept, and advances in understanding this process provide new potential therapeutic targets towards the treatment of metabolic disorders.
Abstract: Translation of nutrient stimuli through intracellular signaling is important for adaption and regulation of metabolic processes, while deregulation by either genetic or environmental factors predisposes towards the development of metabolic disorders. Besides providing energy, fatty acids act as prominent signaling molecules by altering cell membrane struc- tures, affecting the lipid modification status of pro- teins, and by modulating ligand-activated nuclear receptor activity. Given their highly hydrophobic nature, fatty acids in the aqueous intracellular com- partment are bound to small intracellular lipid binding proteins which function as intracellular carriers of these hydrophobic components. This review describes recent advances in identifying intracellular pathways for cytosolic fatty acid signaling through ligand- activated receptors by means of small intracellular lipid binding proteins. The mechanism behind intra- cellular fatty acid transport and subsequent nuclear receptor activation is an emerging concept, and advances in understanding this process provide new potential therapeutic targets towards the treatment of metabolic disorders.
TL;DR: It is suggested that intracellular lipid-binding proteins such as I-FABP may enhance the membrane transport of lipophilic xenobiotics and facilitate drug access to the enterocyte cytoplasm and cy toplasmic organelles.
TL;DR: The mechanism behind intracellular fatty acid transport and subsequent nuclear receptor activation is an emerging concept, and advances in understanding this process provide new potential therapeutic targets towards the treatment of metabolic disorders.
Abstract: Translation of nutrient stimuli through intracellular signaling is important for adaption and regulation of metabolic processes, while deregulation by either genetic or environmental factors predisposes towards the development of metabolic disorders. Besides providing energy, fatty acids act as prominent signaling molecules by altering cell membrane structures, affecting the lipid modification status of proteins, and by modulating ligand-activated nuclear receptor activity. Given their highly hydrophobic nature, fatty acids in the aqueous intracellular compartment are bound to small intracellular lipid binding proteins which function as intracellular carriers of these hydrophobic components. This review describes recent advances in identifying intracellular pathways for cytosolic fatty acid signaling through ligand activated receptors by means of small intracellular lipid binding proteins. The mechanism behind intracellular fatty acid transport and subsequent nuclear receptor activation is an emerging concept, and advances in understanding this process provide new potential therapeutic targets towards the treatment of metabolic disorders.
TL;DR: It is shown that genetic variability at the FABP4 locus has been shown to be associated with plasma lipid levels, type 2 diabetes, and coronary heart disease risk.
Abstract: Fatty acid binding proteins (FABPs) are proteins that reversibly bind fatty acids and other lipids. So far, nine tissue-specific cytoplasmic FABPs have been identified. Adipose tissue FABP (FABP4) has been suggested to be a bridge between inflammation and other pathways related to the metabolic syndrome. In this regard, genetic variability at the FABP4 locus has been shown to be associated with plasma lipid levels, type 2 diabetes, and coronary heart disease risk.
TL;DR: The results suggest that enterocytes might regulate intrACEllular FABP content in response to intracellular fatty acids, which it is speculated may act as lipid sensors to prevent their intracesllular transport.
Abstract: We investigated, for the first time, the expression of I- and L-FABP in two very rare hereditary lipid malabsorption syndromes as compared with normal subjects. Abetalipoproteinemia (ABL) and Anderson's disease (AD) are characterized by an inability to export alimentary lipids as chylomicrons that result in fat loading of enterocytes. Duodeno-jejunal biopsies were obtained from 14 fasted normal subjects, and from four patients with ABL and from six with AD. Intestinal FABP expression was investigated by immuno-histochemistry, western blot, ELISA and Northern blot analysis. In contrast to normal subjects, the cellular immunostaining for both FABPs was clearly decreased in patients, as the enterocytes became fat-laden. In patients with ABL, the intestinal contents of I- (60.7 +/- 13.38 ng/mg protein) and L-FABP (750.3 +/- 121.3 ng/mg protein) are significantly reduced (50 and 35%, P < 0.05, respectively) as compared to normal subjects (I-135.3 +/- 11.1 ng, L-1211 +/- 110 ng/mg protein). In AD, the patients also exhibited decreased expression (50%, P < 0.05; I-59 +/- 11.88 ng, L-618.2 +/- 104.6 ng/mg protein). Decreased FABP expression was not associated with decreased mRNA levels. The results suggest that enterocytes might regulate intracellular FABP content in response to intracellular fatty acids, which we speculate may act as lipid sensors to prevent their intracellular transport.
TL;DR: Although the domains can widen enough to allow the passage of palmitate, fatty acid release through the helical portal region incurs smaller conformational changes and a lower energetic cost.
Abstract: Intestinal fatty acid binding protein (IFABP) interacts with biological membranes and delivers fatty acid (FA) into them via a collisional mechanism. However, the membrane-bound structure of the protein and the pathway of FA transfer are not precisely known. We used molecular dynamics (MD) simulations with an implicit membrane model to determine the optimal orientation of apo- and holo-IFABP (bound with palmitate) on an anionic membrane. In this orientation, the helical portal region, delimited by the αII helix and the βC-βD and βE-βF turns, is oriented toward the membrane whereas the putative β-strand portal, delimited by the βB-βC, βF-βG, βH-βI turns and the N terminus, is exposed to solvent. Starting from the MD structure of holo-IFABP in the optimal orientation relative to the membrane, we examined the release of palmitate via both pathways. Although the domains can widen enough to allow the passage of palmitate, fatty acid release through the helical portal region incurs smaller conformational changes and a lower energetic cost.
TL;DR: The present findings suggest that A-FABP and its ligands, fatty acids, play an important role in the process of apoptosis and the immune modulation induced by DEX.
Abstract: Fatty acids have a great influence on the process of lymphocyte apoptosis which is considered as a modulating factor of immune response in both humans and animals. However the mechanism underlying the function of fatty acids in the process of lymphocyte apoptosis is not fully understood. In this study we show that the appearance of adipocyte-type fatty acid binding protein (A-FABP) is induced upon administration of dexamethasone (DEX) in both in vivo and cultured lymphocytes, and its distinct nuclear localization occurs in close relation to the DEX-induced apoptosis process. In immuunohistochemistry of mouse spleen, A-FABP-immunoreactivity starts to occur 3 h after DEX stimulation, and it massively localizes in the nucleus 8 h after the treatment, while no A-FABP-immunoreactivity is discerned in the lymphocytes of normal as well as 24 h post-injection spleen. In the murine T-cell leukemia CTLL-2 cells, A-FABP-immunoreactivity is also induced in both of the cytoplasm and nucleus when the apoptosis is induced by IL-2 retrieval together with DEX treatment, while in the presence of IL-2 A-FABP-immunoreactivity is confined to the cytoplasm with DEX trreatment. On the other hand, A-FABP-immunoreactivity is not detected by IL-2 retrieval alone. The present findings altogether suggest that A-FABP and its ligands, fatty acids, play an important role in the process of apoptosis and the immune modulation induced by DEX.
TL;DR: The effect of dietary fatty acids on the populational pattern of insulin resistance is not independent of the Ala54Thr polymorphism of FABP2, and an interaction existed between this polymorphism and the intake of dietary fats in a population with a high intake of monounsaturated fatty acids.
TL;DR: This study explores inhibiting FABP4/aP2 as a strategy for treating atherosclerosis and type 2 diabetes.
TL;DR: Depletion of plasma membrane cholesterol reversibly inhibited oleate uptake by adipocytes without altering the amount or the cell surface distribution of either caveolin-1 or CD36.
TL;DR: It is demonstrated that C. trachomatis can productively infect liver cells and utilize FABP-transported LCFA for its own biosynthesis.
Abstract: Chlamydia trachomatis is an obligate intracellular bacterium and acquires both building blocks and energy from host cells for growth. The fatty acid-binding protein (FABP) plays an important role in uptake of long-chain fatty acids (LCFA) and energy metabolism by eukaryotic cells. The roles of FABP and LCFA in chlamydial infection were evaluated. Infection of liver cells with chlamydial organisms promoted fatty acid uptake by the infected cells, suggesting that LCFA may benefit chlamydial growth. Introduction of FABP into the liver cells not only enhanced fatty acid uptake, but also increased chlamydial intravacuolar replication and maturation. The FABP-enhanced chlamydial intracellular growth was dependent on the host cell uptake of fatty acids. These results have demonstrated that C. trachomatis can productively infect liver cells and utilize FABP-transported LCFA for its own biosynthesis.
TL;DR: The crystal structure of Rv0813c reveals a new family of proteins that resemble the fatty acid-binding proteins (FABPs) found in eukaryotes, and is suggested to have roles in the recognition, transport, and/or storage of small molecules in the bacterial cytosol.
Abstract: The gene Rv0813c from Mycobacterium tuberculosis, which codes for a hypothetical protein of unknown function, is conserved within the order Actinomycetales but absent elsewhere. The crystal structure of Rv0813c reveals a new family of proteins that resemble the fatty acid-binding proteins (FABPs) found in eukaryotes. Rv0813c adopts the 10-stranded beta-barrel fold typical of FABPs but lacks the double-helix insert that covers the entry to the binding site in the eukaryotic proteins. The barrel encloses a deep cavity, at the bottom of which a small cyclic ligand was found to bind to the hydroxyl group of Tyr192. This residue is part of a conserved Arg-X-Tyr motif much like the triad that binds the carboxylate group of fatty acids in FABPs. Most of the residues forming the internal surface of the cavity are conserved in homologous protein sequences found in CG-rich prokaryotes, strongly suggesting that Rv0813c is a member of a new family of bacterial FABP-like proteins that may have roles in the recognition, transport, and/or storage of small molecules in the bacterial cytosol.
TL;DR: Two major transport functions for fatty acid binding proteins (FABPs), one of the most commonly studied examples of this diverse class, are clarified and it is concluded that they serve complementary intracellular transport functions.
Abstract: Cytosolic binding proteins are ubiquitous, yet their functions have been poorly defined. Research in multiple labs has now clarified two major transport functions for fatty acid binding proteins (FABPs), one of the most commonly studied examples of this diverse class. Most cellular fatty acids are bound to membranes. Because fatty acids are almost insoluble in water, their movement across the water between cellular membranes is very slow without FABP. FABP increases this rate by increasing the solubility of fatty acids in water. Many forms of FABP can also increase this rate by catalyzing release of the fatty acids from membranes. The first function is most valuable over longer distances (e.g., >1 μm in rat liver cells), while the second is most valuable for shorter distances. Thus, FABPs serve complementary intracellular transport functions. These conclusions may apply to other cytosolic proteins that bind poorly-soluble molecules.