Lipid transfer proteins

doi:10.1016/0009-3084(90)90083-4

Chemistry and Physics of Lipids

Volume 56, Issue 1, November 1990, Pages 1-20

https://doi.org/10.1016/0009-3084(90)90083-4 Get rights and content

Abstract

Translocations of various lipid species between membranes have been extensively studied. The transport of water-insoluble lipids is thought to require the participation of lipid transfer proteins (LTP). Several LTP, differing in their physicochemical properties and substrate specificities, have been purified to homogeneity from blood plasma, eucaryotic and procaryotic cells. Depending on their site of activity, they can be classified as extracellular and intracellular LTP. Extracellular LTP are found in the blood plasma and intracellular LTP, which were originally characterized as phospholipid exchange proteins, are ubiquitous in nature. Despite the enormous knowledge about their physicochemical properties and their function in vitro their physiological role has not been clearly demonstrated. However, their ubiquitous occurrence indicates an important role in cellular events. This review gives an overview of this interesting category of proteins, which are able to catalyze inter-membrane transfer and exchange of lipids.

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Computational evaluation on the binding affinity of non-specific lipid-transfer protein-2 with fatty acids
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Citation Excerpt :
Lipid transfer proteins (LTPs) are typically present in the majority of prokaryotic and eukaryotic cells [1] such as bacteria, yeasts, plants and animals [2].
A computational study was carried out to identify the structural determinant controlling the affinity, specificity and binding strength of several saturated and unsaturated fatty acids with Oryza sativa (Indica group) nonspecific lipid transfer protein (nsLTP2). Association between the number, position and conformation of hydrophobic patches and lipid binding properties of the protein was evidenced by docking analysis. Binding affinity is influenced by the number of carbon atoms, location of double bonds and hydroxyl group in the acyl chain. The results may direct at developing applications in LTP-mediated transport and controlled release of low molecular weight drugs.
Mitochondrial kinases and their molecular interaction with cardiolipin
2009, Biochimica et Biophysica Acta - Biomembranes
Citation Excerpt :
We have recently shown that MtCK and NDPK-D facilitate the transfer of lipids between these membranes [59]. Transfer of lipids between bilayers is more commonly facilitated by specific lipid transfer proteins [194–196]. However, there is a report indicating that t-Bid also has lipid transfer activity [197], but this may be a result of its structural similarity to other lipid transfer proteins [198].
Mitochondrial isoforms of creatine kinase (MtCK) and nucleoside diphosphate kinase (NDPK-D) are not phylogenetically related but share functionally important properties. They both use mitochondrially generated ATP with the ultimate goal of maintaining proper nucleotide pools, are located in the intermembrane/cristae space, have symmetrical oligomeric structures, and show high affinity binding to anionic phospholipids, in particular cardiolipin. The structural basis and functional consequences of the cardiolipin interaction have been studied and are discussed in detail in this review. They mainly result in a functional interaction of MtCK and NDPK-D with inner membrane adenylate translocator, probably by forming proteolipid complexes. These interactions allow for privileged exchange of metabolites (channeling) that ultimately regulate mitochondrial respiration. Further functions of the MtCK/membrane interaction include formation of cardiolipin membrane patches, stabilization of mitochondria and a role in apoptotic signaling, as well as in case of both kinases, a role in facilitating lipid transfer between two membranes. Finally, disturbed cardiolipin interactions of MtCK, NDPK-D and other proteins like cytochrome c and truncated Bid are discussed more generally in the context of apoptosis and necrosis.
Novel lipid transfer property of two mitochondrial proteins that bridge the inner and outer membranes
2007, Biophysical Journal
Citation Excerpt :
In this work, we have studied whether these kinases are able to facilitate lipid transfer between membranes, as this could be a novel functional property of the two proteins. Transfer of lipids between bilayers is only known to be facilitated by specific lipid transfer proteins (11–13). There is a report indicating that t-Bid has lipid transfer activity (14), but this is suggested to be a result of its structural similarity to other lipid transfer proteins (15).
This study provides evidence of a novel function for mitochondrial creatine kinase (MtCK) and nucleoside diphosphate kinase (NDPK-D). Both are basic peripheral membrane proteins with symmetrical homo-oligomeric structure, which in the case of MtCK was already shown to allow crossbridging of lipid bilayers. Here, different lipid dilution assays clearly demonstrate that both kinases also facilitate lipid transfer from one bilayer to another. Lipid transfer occurs between liposomes mimicking the lipid composition of mitochondrial contact sites, containing 30 mol % cardiolipin, but transfer does not occur when cardiolipin is replaced by phosphatidylglycerol. Ubiquitous MtCK, but not NDPK-D, shows some specificity in the nature of the lipids transferred and it is not active with phosphatidylcholine alone. MtCK can undergo reversible oligomerization between dimeric and octameric forms, but only the octamer can bridge membranes and promote lipid transfer. Cytochrome c, another basic mitochondrial protein known to bind to anionic membranes but not crosslinking them, is also incapable of promoting lipid transfer. The lipid transfer process does not involve vesicle fusion or loss of the internal contents of the liposomes.
Lipid metabolism, atherogenesis and CD1-restricted antigen presentation
2006, Trends in Molecular Medicine
CD1 molecules are a family of major histocompatibility complex (MHC)-related glycoproteins that present lipid and glycolipid antigens to T cells. Interestingly, it has been demonstrated that CD1d-restricted T cells have a pathogenic role in atherosclerosis. Recent studies suggest an association between the cellular machinery that loads CD1 molecules with glycolipids and several key proteins in lipid metabolism. These proteins include the sphingolipid activator proteins (SAPs), microsomal triglyceride transfer protein (MTP) and apolipoprotein E (apoE). MTP and SAPs seem to be crucial for loading CD1d with lipids in the endoplasmic reticulum and endosomal compartments, respectively, whereas apoE facilitates efficient uptake and delivery of exogenous lipid antigens to CD1d in endosomal compartments. These studies reveal new and unexpected relationships between lipid metabolism and antigen presentation by CD1 molecules. Targeting this pathway of immune activation might have therapeutic potential for the treatment of chronic inflammatory diseases.
Structural basis of non-specific lipid binding in maize lipid-transfer protein complexes revealed by high-resolution X-ray crystallography
2001, Journal of Molecular Biology
Non-specific lipid-transfer proteins (nsLTPs) are involved in the movement of phospholipids, glycolipids, fatty acids, and steroids between membranes. Several structures of plant nsLTPs have been determined both by X-ray crystallography and nuclear magnetic resonance. However, the detailed structural basis of the non-specific binding of hydrophobic ligands by nsLTPs is still poorly understood. In order to gain a better understanding of the structural basis of the non-specific binding of hydrophobic ligands by nsLTPs and to investigate the plasticity of the fatty acid binding cavity in nsLTPs, seven high-resolution (between 1.3 Å and 1.9 Å) crystal structures have been determined. These depict the nsLTP from maize seedlings in complex with an array of fatty acids.
A detailed comparison of the structures of maize nsLTP in complex with various ligands reveals a new binding mode in an nsLTP-oleate complex which has not been seen before. Furthermore, in the caprate complex, the ligand binds to the protein cavity in two orientations with equal occupancy. The volume of the hydrophobic cavity in the nsLTP from maize shows some variation depending on the size of the bound ligands.
The structural plasticity of the ligand binding cavity and the predominant involvement of non-specific van der Waals interactions with the hydrophobic tail of the ligands provide a structural explanation for the non-specificity of maize nsLTP. The hydrophobic cavity accommodates various ligands from C10 to C18. The C18:1 ricinoleate with its hydroxyl group hydrogen bonding to Ala68 possibly mimics cutin monomer binding which is of biological importance. Some of the myristate binding sites in human serum albumin resemble the maize nsLTP, implying the importance of a helical bundle in accommodating the non-specific binding of fatty acids.
Cloning and expression in phospholipid containing cultures of the gene encoding the specific phosphatidylglycerol/phosphatidylinositol transfer protein from Aspergillus oryzae: Evidence that the pg/pi-tp is tandemly arranged with the putative 3-ketoacyl-CoA thiolase gene
2001, Gene
Citation Excerpt :
In vitro, they facilitate the transfer of phospholipids between naturally or artificially prepared membranes (Wirtz, 1991). They have been classified in to three classes based on their transfer specificity (Rueckert and Schmidt, 1990). Monospecific PLTPs transfer one type of phospholipid (Kamp et al., 1973), oligospecific PLTPs exhibit specificity for more than one type of phospholipid (Lafer et al., 1991), and non-specific PLTPs transfer all varieties of phospholipids and other lipids like cholesterol and glycolipids (Arondel and Kader, 1990).
The phosphatidylglycerol/phosphatidylinositol transfer protein (PG/PI-TP) is a new and original phospholipid transfer protein (PLTP) isolated from the Deuteromycete, Aspergillus oryzae. We have isolated a genomic clone of the A. oryzae pg/pi-tp using a probe derived from the corresponding cDNA and sequenced the complete gene. The DNA sequence analysis revealed that pg/pi-tp gene is composed of three exons encoding a 18,823 Da protein of 175 amino acids as previously described and of two introns as deduced by cDNA and genomic sequence alignment. The isolated pg/pi-tp gene do not show similarity with other PLTP genes or the deduced PG/PI-TP protein with proteins already known. Comparison of the encoded PG/PI-TP with other deduced proteins from recent genomic or cDNA sequence from databases revealed that the PG/PI-TP was close to two encoded proteins deduced from the cDNA database of Aspergillus nidulans (54% identity and 68% similarity) and the second from Neurospora crassa (53% identity and 76% similarity). Therefore, we suggested that both proteins might belong to the PLTP family. Southern blot analysis of A. oryzae genomic DNA show that the PG/PI-TP was encoded by a single gene. Expression of pg/pi-tp was performed in phospholipid containing cultures with increasing carbon source concentrations in order to study the regulation of the PLTPs in the filamentous fungus cell. This was done to know if a high density culture could yield a high amount of biomass with high phospholipid transfer activity. Results showed that phospholipids as compared to glucose in standard cultures stimulated mycelial growth and global phospholipid transfer activity, but not the pg/pi-tp transcript accumulation. However, high concentration of both carbon sources yielded an inhibition of the expression of the pg/pi-tp gene and of the global phospholipid transfer activity. In conclusion, both carbon sources are not suitable to increase the PLTP production in high density cultures for biotechnological applications. Finally, using the gene walking sequencing method it is demonstrated that the pg/pi-tp is tandemly arranged on opposite DNA strands in a tail-to-tail orientation with a putative gene encoding the 3-ketoacyl-CoA thiolase (EC 2.3.1.16). Unlike the pg/pi-tp gene, this thiolase gene show a putative ‘β-oxidation box’ and encodes a putative 44,150 Da protein of 321 amino acids composed of a putative N-terminal PTS2 (Peroxisomal Targeting Signal) consensus sequence for the peroxisome targeting. Comparison of the amino acid sequence of the A. oryzae thiolase to that of the Yarrowia lipolytica showed a 50% identity and a 69% similarity.

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Review articleLipid transfer proteins

Abstract

Biochim. Biophys. Acta

J. Lipid Res.

Cell Surface Rev.

Chem. Phys. Lipids

Chem. Phys. Lipids

Chem. Phys. Lipids

New Comprehensive Biochemistry

Prog. Lipid Res.

Adv. Lipid Res.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Atherosclerosis

Biochim. Biophys. Acta

Metabolism

Metabolism

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

J. Lipid Res.

Methods Enzymol.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Lipid Res.

J. Biol. Chem.

Atherosclerosis

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Methods Enzymol.

Artherosclerosis

J. Lipid Res.

Atherosclerosis

Biochim. Biophys. Acta

J. Biol. Chem.

Atherosclerosis

J. Lipid Res.

J. Biol. Chem.

FEBS Lett.

J. Biol. Chem.

Biochim. Biophys. Acta

FEBS Lett.

J. Lipid Res.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

J. Biol. Chem.

Review article
Lipid transfer proteins