Lipid transfer proteins enhance cell wall extension in tobacco

Plant cells are enclosed by a rigid cell wall that counteracts the internal osmotic pressure of the vacuole and limits the rate and direction of cell enlargement. When developmental or physiological cues induce cell extension, plant cells increase wall plasticity by a process called loosening. It was demonstrated previously that a class of proteins known as expansins are mediators of wall loosening. Here, we report a type of cell wall-loosening protein that does not share any homology with expansins but is a member of the lipid transfer proteins (LTPs). LTPs are known to bind a large range of lipid molecules to their hydrophobic cavity, and we show here that this cavity is essential for the cell wall-loosening activity of LTP. Furthermore, we show that LTP-enhanced wall extension can be described by a logarithmic time function. We hypothesize that LTP associates with hydrophobic wall compounds, causing nonhydrolytic disruption of the cell wall and subsequently facilitating wall extension.     

Lipid transfer proteins in the study of artificial and natural membranes

Summary Lipid transfer proteins, differing in their specificity for the transfer of lipids and for the surfaces on which they act, have been purified from various mammalian tissues and subsequently characterized. Several of their properties make them useful research tools. They have been used alone or with other techniques to study the distribution and mobility of phospholipids in artificial vesicles and in natural membranes, and have been used to create asymmetric phospholipid vesicles.Lipid transfer proteins are capable of altering the lipid composition of membranes by introducing new lipids or by depletion of existing lipids. Some of the transfer proteins can effect a net transfer of phospholipids, glycosphingolipids and cholesterol from one structure to another, whereas others appear to act primarily in promoting exchange. Some lipid transfer proteins are capable of introducing spin labeled and fluorescent lipid analogs into the outer surface of membranes. Because lipid transfer proteins do not seem to alter membrane lipid asymmetry or permeability of membranes, they are useful tools for studying the effect of lipid substitution on membrane-mediated transport processes and on various membrane-bound enzyme systems.Abbreviations PA phosphatidic acid - PC phosphatidylcholine - PE phosphatidylethanolamine - PI phosphatidylinositol - PG phosphatidylglycerol - PS phosphatidylserine - DPG diphosphatidylglycerol - SPH sphingomyelin - G_{m t} II³--N-Acetylneuraminosylgangliotetraglycosylceramide - GbOse₄Cer globotetraglycosylceramide Career Investigator of C.O.N.I.C.E.T. (Argentina)Career Investigator of the American Heart Association.     

Lipid transfer proteins from Rosaceae fruits share consensus epitopes responsible for their IgE-binding cross-reactivity

Four IgE-binding epitopes have been characterized that cover a large area (40%) of the molecular surface of lipid transfer protein allergens of Rosaceae (apple, peach, apricot, and plum). They mainly correspond to electropositively charged regions protruding on the molecular surface of the modeled apple (Mal d 3), apricot (Pru ar 3), and plum (Pru d 3) allergens. Two of these epitopes consist of consensus epitopes structurally conserved among the lipid transfer protein allergens from the Rosaceae. Their occurrence in different lipid transfer protein allergens presumably accounts for the IgE-binding cross-reactivity often observed among different Rosaceae fruits. In this respect, LTP consist of phylogenetically- and structurally-related pan allergens. However, the IgE-binding cross-reactivity due to fruit lipid transfer protein has varying degrees of clinical relevance and this cross-reactivity is not necessarily accompanied by a cross-allergenicity to the corresponding fruits.     

Lipid oxidation in biological membranes. Electron transfer proteins as initiators of lipid autoxidation.

Biological lipid autoxidation has been studied in a model system composed of sonicated phospholipids as substrate and electron transfer proteins found in membranes as possible catalysts. Heme compounds, flavoproteins, and iron-sulfur proteins were examined for their ability to initiate lipid autoxidation. Among many heme compounds tested, the most active were hematin ?microperoxidase ? methemoglobin > cytochrome c. With fresh preparations of phospholipids, reaction rates (nanomoles of oxygen/minute nanomoles of heme) ranged from 5 (cytochrome c) to 350 (hematin). Only the oxidized heme compounds were active as catalysts. Reduced heme compounds, flavoproteins and riboflavin were inactive. In the presence of heme compounds, aged preparations of sonicated phospholipids were much more rapidly oxidized than fresh preparations. They also had a higher content of fatty acid hydroperoxides as judged from their characteristic diene absorption peak at 234 nm. This observation agrees with the postulated mechanism of lipid autoxidation by heme compounds, namely, homolytic scission of preformed fatty acid hydroperoxides. Iron-sulfur proteins were also active as initiators of lipid autoxidation when destabilized in the presence of an appropriate iron chelator (o-phenanthroline or 2,2′-bipyridine) or a chaotropic ion. Oxygen uptake rates (nanomoles of oxygen/minute × milligrams of protein) varied from about 200 for an iron-sulfur protein isolated from complex I to about 5500 for Clostridium pasteurianum ferredoxin. However, per nanomole of labile sulfide, the rates for all active iron-sulfur proteins were 4–7 nmol of oxygen/min × nmol of labile sulfide.Superoxide-generating systems did not initiate lipid autoxidation, nor did erythrocuprein inhibit the autoxidations induced by heme compounds or ferredoxin. However, lipid oxidations induced by two other iron-sulfur proteins were partially inhibited by erythrocuprein. It is concluded that in the above system Superoxide anion is neither an initiator nor an obligatory intermediate of lipid autoxidation.     

Lipid transfer proteins in Parietaria judaica L. pollen grains: immunocytochemical localization and function

Parietariajudaica L. (Urticaceae) pollen is considered one of the most common causes of allergic respiratory symptoms in the Mediterranean area. The localization of lipid transfer proteins (LTPs) in P. judaica mature and hydrated-activated pollen grains was investigated applying a combination of transmission electron microscopy (TEM) with immunocytochemical methods. Our results show that the content of LTPs in P. judaica pollen grains changes during the process of hydration. The localization of judaica LTPs in the cytoplasm and in the lipid bodies associated with vacuoles demonstrated that LTPs represent primarily intracellular proteins. On the other hand, exposure of the pollen grains to germination medium induced the release of LTPs from the pollen grain. Thus, LTPs are cytoplasmic proteins that are secreted to become available for pollen-stigma interactions and probably induce the IgE antibody responses in allergic patients.     

Lipid carrier proteins and ethanol

Ethanol has a pronounced effect on lipid homeostasis. It is our overall hypothesis that certain lipid carrier proteins are targets of acute and chronic ethanol exposure and that perturbation of these proteins induces lipid dysfunction leading to cellular pathophysiology. These proteins include both intracellular proteins and lipoproteins. This paper examines recent data on the interaction of ethanol with these proteins. In addition, new data are presented on the stimulatory effects of ethanol on low-density-lipoprotein (LDL)-mediated cholesterol uptake into fibroblasts and direct perturbation of the LDL apolipoprotein, apolipoprotein B. A cell model is presented that outlines potential mechanisms thought to be involved in ethanol perturbation of cholesterol transport and distribution.     

Glycolipid transfer proteins

Glycolipid transfer proteins (GLTPs) are small (24 kDa), soluble, ubiquitous proteins characterized by their ability to accelerate the intermembrane transfer of glycolipids in vitro. GLTP specificity encompasses both sphingoid- and glycerol-based glycolipids, but with a strict requirement that the initial sugar residue be beta-linked to the hydrophobic lipid backbone. The 3D architecture of GLTP reveals liganded structures with unique lipid-binding modes. The biochemical properties of GLTP action at the membrane surface have been studied rather comprehensively, but the biological role of GLTP remains enigmatic. What is clear is that GLTP differs distinctly from other known glycolipid-binding proteins, such as nonspecific lipid transfer proteins, lysosomal sphingolipid activator proteins, lectins, lung surfactant proteins as well as other lipid-binding/transfer proteins. Based on the unique conformational architecture that targets GLTP to membranes and enables glycolipid binding, GLTP is now considered the prototypical and founding member of a new protein superfamily in eukaryotes.     

Lipid droplet proteins and metabolic diseases

Lipid droplets (LDs) are ubiquitous cellular organelles for lipid storage which are composed of a neutral lipid core bounded by a protein decorated phospholipid monolayer. Although lipid storage is their most obvious function, LDs are far from inert as they participate in maintaining lipid homeostasis through lipid synthesis, metabolism, and transportation. Furthermore, they are involved in cell signaling and other molecular events closely associated with human disease such as dyslipidemia, obesity, lipodystrophy, diabetes, fatty liver, atherosclerosis, and others. The last decade has seen a great increase in the attention paid to LD biology. Regardless, many fundamental features of LD biology remain obscure. In this review, we will discuss key aspects of LD biology including their biogenesis, growth and regression. We will also summarize the current knowledge about the role LDs play in human disease, especially from the perspective of the dynamics of the associated proteins. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.     

Lipid outward translocation by ABC proteins

In humans, about 50 ABC proteins play physiologically important roles. Many ABC proteins are involved in lipid outward translocation and lipid homeostasis in the body, and defects in their functions cause various diseases. However, the precise mechanisms of substrate transport remain unclear. In bacteria, several ABC proteins are involved in the transport of lipoproteins and lipopolysaccharides from the inner to outer membrane, and their functioning is a prerequisite for survival. Their functions can be divided into “flip-flop” and “projection”. In this review, human ABC proteins are compared to bacterial proteins to elucidate their mechanisms.     

Lipid transport by mammalian ABC proteins

ABC (ATP-binding cassette) proteins actively transport a wide variety of substrates, including peptides, amino acids, sugars, metals, drugs, vitamins and lipids, across extracellular and intracellular membranes. Of the 49 hum an ABC proteins, a significant number are known to mediate the extrusion of lipids from membranes or the flipping of membrane lipids across the bilayer to generate and maintain membrane lipid asymmetry. Typical lipid substrates include phospholipids, sterols, sphingolipids, bile acids and related lipid conjugates. Members of the ABCA subfamily of ABC transporters and other ABC proteins such as ABCB4, ABCG1 and ABCG5/8 implicated in lipid transport play important roles in diverse biological processes such as cell signalling, membrane lipid asymmetry, removal of potentially toxic compounds and metabolites, and apoptosis. The importance of these ABC lipid transporters in cell physiology is evident from the finding that mutations in the genes encoding many of these proteins are responsible for severe inherited diseases. For example, mutations in ABCA1 cause Tangier disease associated with defective efflux of cholesterol and phosphatidylcholine from the plasma membrane to the lipid acceptor protein apoA1 (apolipoprotein AI), mutations in ABCA3 cause neonatal surfactant deficiency associated with a loss in secretion of the lipid pulmonary surfactants from lungs of newborns, mutations in ABCA4 cause Stargardt macular degeneration, a retinal degenerative disease linked to the reduced clearance of retinoid compounds from photoreceptor cells, mutations in ABCA12 cause harlequin and lamellar ichthyosis, skin diseases associated with defective lipid trafficking in keratinocytes, and mutations in ABCB4 and ABCG5/ABCG8 are responsible for progressive intrafamilial hepatic disease and sitosterolaemia associated with defective phospholipid and sterol transport respectively. This chapter highlights the involvement of various mammalian ABC transporters in lipid transport in the context of their role in cell signalling, cellular homoeostasis, apoptosis and inherited disorders.     

Plasma lipid transfer proteins

PURPOSE OF REVIEW: Plasma cholesteryl ester transfer protein and phospholipid transfer protein are involved in lipoprotein metabolism. Conceivably, manipulation of either transfer protein could impact atherosclerosis and other lipid-driven diseases. RECENT FINDINGS: Cholesteryl ester transfer protein mediates direct HDL cholesteryl ester delivery to the liver cells; adipose tissue-specific overexpression of cholesteryl ester transfer protein in mice reduces the plasma HDL cholesterol concentration and adipocyte size; cholesteryl ester transfer protein TaqIB polymorphism is associated with HDL cholesterol plasma levels and the risk of coronary heart disease. In apolipoprotein B transgenic mice, phospholipid transfer protein deficiency enhances reactive oxygen species-dependent degradation of newly synthesized apolipoprotein B via a post-endoplasmic reticulum process, as well as improving the antiinflammatory properties of HDL in mice. Activity of this transfer protein in cerebrospinal fluid of patients with Alzheimer's disease is profoundly decreased and exogenous phospholipid transfer protein induces apolipoprotein E secretion by primary human astrocytes in vitro. SUMMARY: Understanding the relationship between lipid transfer proteins and lipoprotein metabolism is expected to be an important frontier in the search for a therapy for atherosclerosis.     

Lipid exchange and transfer between biological lipid-protein structures

The dynamic state of membrane and lipoprotein lipids is all the more impressive when the complexity of lipoprotein and membrane structure is considered. For as long as such a ubiquitous and easily demonstrable process has been studied, the mechanism(s) of lipid exchange is still unknown. Is a direct contact between lipoproteins and membranes required for lipid exchange, or are molecules expelled from lipid-protein complexes to spend a transient existence in the aqueous environment before returning to their donor or being accomodated in another complex? Although recent studies suggest the certain proteins such as the phospholipid exchange proteins can exert some vectoral and selective control over exchange reactions, the exchange of lipids, as studied under most conditionsin vitro, seems to be a random occurrence and a purely physicochemical event. Ifin vitro studies are indeed reflective of the processesin vivo, the lipid exchange activity in a cell can likely be depicted as shown in Figure 18.     

Electron transfer proteins/enzymes

The crystal structures of eight electron-carrier proteins, three electron-transfer enzymes and three intermolecular complexes, analyzed during the period of this review, are described. These studies have established the structures of two new metal redox clusters, helped to define the interactions between electron-transfer proteins, and illustrated possible paths for electron flow in these biological systems.     

Electron transfer in ruthenium-modified proteins

Photochemical techniques have been used to measure the kinetics of intramolecular electron transfer in Ru(bpy)₂(im)(His)²⁺-modified (bpy = 2,2-bipyridine; im = imidazole) cytochromec and azurin. A driving-force study with the His33 derivatives of cytochromec indicates that the reorganization energy () for Fe²⁺Ru³⁺ ET reactions is 0.8 eV. Reductions of the ferriheme by either an excited complex,^*Ru²⁺, or a reduced complex, Ru⁺, are anomalously fast and may involve formation of an electronically excited ferroheme. The distance dependence of Fe²⁺Ru³⁺ and Cu⁺Ru³⁺ electron transfer in 12 different Ru-modified cytochromes and azurins has been analyzed using a tunneling-pathway model. The ET rates in 10 of the 12 systems exhibit an exponential dependence on metal-metal separation (decay constant of 1.06 å^–1) that is consistent with predictions of the pathway model.