Putative Lipoprotein Research Articles

The adc locus, which affects competence for genetic transformation in Streptococcus pneumoniae, encodes an ABC transporter with a putative lipoprotein homologous to a family of streptococcal adhesins

To identify new components involved in the phenomenon of transformation in Streptococcus pneumoniae, a library of potential mutants has been generated by random insertion of an erythromycin resistance gene. Transformation-deficient mutants were screened using an in situ colony transformation test. The adc locus, which was identified in this search, was cloned and sequenced. Sequence analysis revealed a putative operon of three ORFs (adcC, adcB and adcA) with homology to ATP-binding cassette (ABC) transport operons encoding streptococcal adhesins such as ScaA of S. gordonii and FimA of S. parasanguis. adcA can encode a lipoprotein of 313 amino acid residues containing a putative metal-binding site. The polypeptide shows about 30% sequence identity with ScaA and FimA. We discuss evidence which leads us to propose that AdcA, together with a set of 14 proteins including ScaA, FimA and homologous adhesins, defines a new family of external solute-binding proteins, cluster 9, specific for metals.

Overexpression of the mexC-mexD-oprJ efflux operon in nfxB-type multidrug-resistant strains of Pseudomonas aeruginosa.

OprJ, overproduced in nfxB multidrug-resistant strains of Pseudomonas aeruginosa, and OprK, overproduced in the multidrug-resistant strain K385, were demonstrated to be immunologically cross-reactive using an OprJ-specific monoclonal antibody. Treatment of the purified proteins with trypsin or chymotrypsin yielded virtually indistinguishable digestion patterns, and the N-terminal sequence of two trypsin fragments was identical for both proteins, indicating that OprJ and OprK share identity. The N-terminal amino acid sequences were used to facilitate cloning of the oprJ gene on a 5kbp Kpnl fragment and a 10 kbp BamHl fragment. Nucleotide sequencing of portions of these fragments revealed that oprJ was the terminal gene in a putative three-gene operon, mexC-mexD-oprJ. The predicted mexC-mexD-oprJ gene products exhibit homology to the MexA-MexB-OprM components of the multidrug-resistance efflux pump of P. aeruginosa (43-46% identity). Consistent with an implied role for mexC-mexD-oprJ in drug efflux, the mexC-mexD-oprJ-hyperexpressing strain K385 showed reduced accumulation of a variety of antibiotics as compared with its parent strain, and this drug 'exclusion' was abrogated by energy inhibitors. The mexC and oprJ products are putative lipoproteins of a molecular mass of 40,707 and 51,742 Da, respectively, while mexD was predicted to encode a protein of 111 936 Da. Sequencing upstream of mexC revealed the presence of the nfxB gene transcribed divergently from the efflux genes. Overproduction of OprJ and the attendant multiple-antibiotic resistance of strain K385 was shown to result from a point mutation in nfxB, resulting in a H87-->R change in the predicted NfxB polypeptide. OprJ overproduction and multidrug resistance in K385 was reversed by the cloned nfxB gene, suggesting that nfxB encodes a repressor of mexC-mexD-oprJ expression. Consistent with this, the cloned nfxB gene repressed synthesis of a mexC-lacZ fusion in Escherichia coli. nfxB also repressed expression of a nfxB-lacZ fusion, indicating that NfxB negatively regulates its own expression. These data indicate that the multidrug resistance of nfxB strains is due to overexpression of an efflux operon, mexC-mexD-oprJ, encoding components of a second efflux pump in P. aeruginosa.

Immunity to lantibiotics

Bacteria producing bacteriocins have to be protected from being killed by themselves. This mechanism of self-protection or immunity is especially important if the bacteriocin does not need a specific receptor for its action, as is the case for the type A lantibiotics forming pores in the cytoplasmic membrane. At least two different systems of immunity have evolved in this group of bacteriocins containing modified amino acids as a result of posttranslational modification. The immunity mechanism of Pep5 in Staphylococcus epidermidis is based on inhibition of pore formation by a small 69-amino acid protein weakly associated with the outer surface of the cytoplasmic membrane. In Lactococcus lactis and Bacillus subtilis the putative immunity lipoproteins NisI and SpaI, respectively, are also located at the outer surface of the cytoplasmic membrane, suggesting that a similar mechanism might be utilized by the producers of nisin and subtilin. In addition an ABC-transport system consisting of two membrane proteins, (NisEG, SpaG and the hydrophobic domain of SpaF, and EpiEG) and a cytoplasmic protein (NisF, the cytoplasmic domain of SpaF, and EpiF) play a role in immunity of nisin, subtilin and epidermin by import, export or inhibition of pore formation by the membrane components of the transport systems. Almost nothing is known of the immunity determinants of newly described and other type of lantibiotics.

MlpA, a lipoprotein required for normal development of Myxococcus xanthus

The mlpA gene encoding a 236-residue polypeptide has been identified immediately downstream of the oar gene of Myxococcus xanthus (M. Martinez-Canamero, J. Munoz-Dorado, E. Farez-Vidal, M. Inouye, and S. Inouye, J. Bacteriol. 175:4756-4763, 1993). The amino-terminal 21 residues of MlpA encode a typical prokaryotic signal sequence with a putative lipoprotein cleavage site. When expressed in Escherichia coli in the presence of [2-3H]glycerol, 3H-labeled MlpA had a molecular mass of 33 kDa and was found to be associated with the membrane fraction. Globomycin, an inhibitor of signal peptidase II, caused a shift in the mobility of E. coli-expressed MlpA to 35 kDa. Subsequently, a mlpA disruption strain (oar+) was constructed and found to have delayed fruiting body formation (by approximately 36 h), with significantly larger fruiting bodies being produced compared with those of the wild-type strain. Nevertheless, spore yields for the two strains were identical after 120 h of development. These data indicate that MlpA, the lipoprotein identified in M. xanthus, is required for normal fruiting body formation.

A highly immunogenic putative Mycobacterium kansasii lipoprotein.

The resurgence of tuberculosis, the emergence of multiple drug resistant tuberculosis, and the increasing prevalence of mycobacterial disease in AIDS patients have increased the importance of defining new mycobacterial antigens that can be utilized in the development of improved diagnostic reagents and more effective vaccines. In this report, a highly immunogenic Mycobacterium kansasii protein (MK35) and the gene encoding this antigen were characterized. MK35 gene probes reacted with genomic DNA from M. avium, M. bovis BCG, M. intracellulare and M. tuberculosis but not with DNA isolated from nine other mycobacterial species. Nucleotide sequence analysis showed that the MK35 gene encodes a 26 kDa protein which contains a consensus bacterial lipoprotein processing sequence. In addition, detergent-phase separation studies strongly suggested that MK35 is a lipoprotein. Skin test assays demonstrated that MK35 elicited a strong response in guinea pigs sensitized with M. kansasii but did not react in M. tuberculosis-sensitized guinea pigs. These results further suggest that mycobacterial lipoproteins are immunogenic antigens that should be considered in the development of new mycobacterial vaccines and diagnostic reagents.

Molecular cloning and immunological characterization of a novel linear-plasmid-encoded gene, pG, of Borrelia burgdorferi expressed only in vivo

Previously we have found that sera from immunocompetent mice infected either naturally by ticks or experimentally with low numbers of Borrelia burgdorferi ZS7 bacteria lack OspA- and OspB-specific antibodies but confer optimal protection on severe combined immunodeficiency mice against challenge with spirochetes (U.E. Schaible, L. Gern, R. Wallich, M. D. Kramer, M. Prester, and M. M. Simon, Immunol. Lett. 36:219-226, 1993). We have now used the latter immune sera to identify new spirochetal structures with relevance for protection from an expression library of the virulent European strain B. burgdorferi ZS7. Here we report the cloning and characterization of a novel lipoprotein, designated pG, the gene for which is located on a 48-kb linear plasmid. Sequence analysis of the pG gene revealed an open reading frame encoding a putative lipoprotein of 196 amino acids with a calculated molecular mass of 22 kDa and a consensus cleavage sequence (Leu-X-Y-Z-Cys) recognized by signal peptidase II. Restriction fragment length polymorphism analyses of pG derived from independent B. burgdorferi isolates from different geographic areas revealed that the gene is species specific, with, however, extensive genotypic heterogeneity. Comparison of the protein sequence of pG with those of other known B. burgdorferi outer surface lipoproteins (OspA to OspF and P27) demonstrated that pG is most related to OspF. Furthermore, the upstream region of pG exhibited extensive sequence homology (> 94%) with the ospEF promoter region. Mouse immune sera to recombinant pG did not recognize a corresponding molecule in lysates of in vitro-propagated ZS7 spirochetes. However, experimental or natural infection of mice with ZS7 resulted in the induction of antibodies with reactivity for pG and the potential to delay the development of clinical arthritis. Together with the finding that sera from Lyme disease patients also contain antibodies to pG, our data suggest that the pG gene is preferentially expressed in the mammal environment.

Molecular cloning of a 46-kilodalton surface antigen (P46) gene from Mycoplasma hyopneumoniae: direct evidence of CGG codon usage for arginine.

The DNA sequence of the gene encoding the early and specific 46-kDa surface antigen (P46) of Mycoplasma hyopneumoniae has been determined. The P46 gene, encoding a putative lipoprotein, contained three TGA codons and a single CGG codon in a 1,257-bp open reading frame. Edman degradation of peptide fragments showed that at least one TGA codon encodes tryptophan and that the CGG codon, which has been reported to be nonsense or unassigned in other mycoplasmas, is used for arginine in M. hyopneumoniae.

Three Highly Homologous Membrane-bound Lipoproteins Participate in Oligopeptide Transport by the Ami System of the Gram-positive Streptococcus pneumoniae

Oligopeptides are an important source of nutrients, but can serve also as signals for intercellular communication. Oligopeptide-binding proteins seem likely to play a role both in oligopeptide transport and in communication processes. One such protein, AmiA, has been identified in Streptococcus pneumoniae. amiA is the first gene of an operon, ami, which encodes a multicomponent oligopeptide transporter belonging to the family of ABC transporters (or traffic ATPases). This transporter was the first system of this type described in Gram-positive bacteria. To investigate the role and the subcellular location of the putative oligopeptide-binding protein in a bacterium devoid of periplasm, AmiA null mutants were first constructed. None was affected for oligopeptide uptake by the Ami system. Since this apparent dispensability of AmiA could result from a functional redundancy, we looked for chromosomal genes encoding homologues of AmiA. Two homologous genes were identified by DNA-DNA hybridization at low stringency with an amiA probe. Both genes (aliA and aliB) were cloned and shown to encode putative lipoproteins highly homologous to AmiA (close to 60% amino acid identity). Examination of all combinations of amiA, aliA and aliB mutations indicated that these proteins have overlapping specificities toward oligopeptides. The triple mutant is as deficient for oligopeptide transport as mutants in the amiCDE or F genes, which demonstrates that an oligopeptide-binding component is absolutely required for transport by the Ami system. Metabolic labelling with [3H]palmitic acid and cell fractionation were used to demonstrate that the three proteins are indeed membrane-bound lipoproteins in S. pneumoniae. This supports our previous hypothesis that substrate-binding lipoproteins are functionally equivalent to the periplasmic substrate-binding component of ABC transporters of Gram-negative bacteria. Finally, the observation that competence for genetic transformation was drastically reduced in a particular AliB mutant suggests that oligopeptide sensing is important for triggering competence.

Screening for mutations in the exon 26 of the apolipoprotein B gene in hypercholesterolemic finnish families by the single-strand conformation polymorphism method

To date, the only known apolipoprotein B (apo B) mutation causing hypercholesterolemia is the apo B 3500 Arg-->Gln or the familial defective apo B (FDB) mutation. This mutation has not been detected in the Finnish population. We have set up a systematic single-strand conformation polymorphism (SSCP) analysis-based screening method to search for other mutations in the exon 26 of the apo B gene in 21 Finnish hypercholesterolemic probands. The 7572-bp exon 26 covers half of the coding region of the gene including the DNA sequence coding for the putative low-density lipoprotein (LDL) receptor binding site on the apo B protein. Exon 26 was amplified as six 1190- to 1435-bp fragments, each of which was further split into three smaller 213- to 579-bp segments by restriction enzymes. These digestion products were run on nondenaturing polyacrylamide gels using at least three different electrophoretic conditions and autoradiographed. All previously known genetic variants in the exon 26 were detected by the SSCP method. A C-->T change at nucleotide 7064, in complete association with the XbaI site, was characterized by direct sequencing. This variant did not affect the amino acid sequence of the apo B protein. The SSCP-based procedure appears suitable for systematic screening for DNA sequence changes in large coding regions.

Effect of apolipoprotein C-I peptides on the apolipoprotein E content and receptor-binding properties of beta-migrating very low density lipoproteins.

To evaluate the role of apolipoprotein (apo) C-I in inhibiting lipoprotein binding to the low density lipoprotein receptor-related protein (LRP), a putative lipoprotein remnant receptor, apoC-peptide fragments were prepared by chemical synthesis or by cyanogen bromide cleavage of intact apoC-I. In ligand-blotting assays, peptides corresponding to residues 1-38, 10-57, 20-57, 30-57, and 40-57 proved ineffective, but intact apoC-I was very effective, at inhibiting the binding of apoE-enriched beta-migrating very low density lipoproteins (beta-VLDL) to the LRP. Studies of the displacement of 125I-labeled apoE from apoE-enriched beta-VLDL showed that the largest peptide (residues 10-57) was two-thirds as effective as intact apoC-I; the other peptides were highly ineffective (residues 40-57, 1-38) or only partly effective (residues 20-57, 30-57). Changes in the intrinsic tryptophan fluorescence and helix content indicated that the largest peptide was similar to apoC-I in lipid binding affinity, while the other peptide fragments showed little or no affinity for either unilamellar or multilamellar vesicles of dimyristoyl-phosphatidylcholine. These findings suggest that the ability of apoC-I fragments to displace apoE from beta-VLDL is largely, but perhaps not exclusively, a reflection of their ability to bind to membranous bilayers and that apoC-I blocking of the interaction between apoE-rich beta-VLDL and the LRP probably involves displacement of a critical amount of the apoE from the surface of this lipoprotein.

Familial Defective Apolipoprotein B-100 Is Clinically Indistinguishable From Familial Hypercholesterolemia

Familial defective apolipoprotein B-100 is caused by a substitution of adenine for guanine in exon 26 of the gene coding for apolipoprotein B, which results in the substitution of glutamine for arginine in the putative low-density lipoprotein-receptor binding domain of the mature protein. This amino acid substitution diminishes the binding capacity of the low-density lipoprotein particle for the low-density lipoprotein receptor, which in turn leads to an increase in levels of plasma total and low-density lipoprotein cholesterol. To identify carriers of this mutation by means of molecular biology techniques in a large cohort of Dutch patients living in the Netherlands and in Canada with primary hypercholesterolemia, to establish the frequency of the disorder, and to investigate its clinical signs and symptoms and the response to cholesterol-lowering therapy. A total of 1248 patients were screened, and the mutation was found in 18 patients who were initially all diagnosed as having familial hypercholesterolemia. Ten of 18 patients had tendon xanthomas or an arcus cornealis or both, and eight of 18 patients had angina or other evidence of coronary artery disease. The disorder was clinically indistinguishable from familial hypercholesterolemia in terms of physical characteristics and lipoprotein measures. Response to lipid-lowering therapy with beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors was similar to that reported in patients with familial hypercholesterolemia. The mutation was associated with a similar haplotype, which was also reported in other patients of Western European descent with familial defective apolipoprotein B100. This strongly suggests that the mutation has a common chromosomal background that originated in Western Europe.

Interaction of apolipoprotein AII with the putative high-density lipoprotein receptor.

There is strong evidence to indicate that binding of HDL by cells is due to recognition of apoproteins residing on the surface of the lipoprotein by the putative HDL receptor(s). Although both of the major HDL apoproteins, AI and AII, are recognized by the putative receptor, the nature of the binding interaction and the domains of the apoproteins involved are largely unknown. Previous data from this laboratory led to the proposal of a model to explain how HDL particles containing AII interacted with the HDL receptor in a different manner as compared to HDL particles which contain apoAI but not apoAII [Vadiveloo, P. K., & Fidge, N. H. (1992) Biochem. J. 284, 145-151]. The model predicted that each chain of the apoAII homodimer contained a binding domain capable of interacting with the HDL receptor. This model was tested in the current study by preparing apoAII monomers, complexing them with phospholipid, and determining the ability of these complexes to bind to putative HDL receptors in rat liver plasma membranes (RLPM) and bovine aortic endothelial cell membranes (BAECM) by ligand blotting. The data showed that these complexes were bound by HB1 and HB2 from RLPM, and to the 110-kDa HDL binding protein from BAECM, providing critical evidence to support the model. Further investigation into the binding interaction revealed that apoAII complexed with phospholipid (apoAII-PC) bound more than delipidated apoAII, which bound more than delipidated apoAII monomers. Thus, optimum binding required the presence of lipid.(ABSTRACT TRUNCATED AT 250 WORDS)

Oar, a 115-kilodalton membrane protein required for development of Myxococcus xanthus

Myxococcus xanthus is a developmental gram-negative bacterium which forms multicellular fruiting bodies upon nutrient starvation. This bacterium was found to contain a 115-kDa membrane protein which separated with the inner membrane fraction by sucrose density gradient centrifugation. The gene for this protein was cloned, and its DNA sequence was determined. The deduced amino acid sequence consists of 1,061 residues. This protein contains a putative signal sequence and many short segments, found scattered throughout the entire protein, that have sequence similarities with OmpA, a major outer membrane protein of Escherichia coli. Thus, the gene was designated oar (OmpA-related protein). A second open reading frame was found 36 bases downstream of the oar termination codon. This open reading frame encodes a protein of 236 residues and contains a putative lipoprotein signal sequence. An aor disruption mutation (delta oar) showed no effect on vegetative growth but caused abnormal morphogenesis during development and reduced myxospore formation. When examined with a light microscope, delta oar cells were unable to aggregate on developmental agar, indicating that Oar is required for cellular adhesiveness during development.

Secretion of the cell surface lipoprotein pullulanase in Escherichia coli. Cooperation or competition between the specific secretion pathway and the lipoprotein sorting pathway

The fatty acid-acylated enzyme pullulanase is normally found in either of two locations in Escherichia coli, depending on whether or not the producing strains also express the genes specifically required for the second step in pullulanase secretion. When they are expressed, the enzyme is localized to the cell surface, while in their absence, it is directed to an unidentified location in the cell envelope which, upon lysis, forms vesicles whose density is intermediate between those of outer and cytoplasmic membrane vesicles. In order to test the role of the putative lipoprotein sorting signal, Asp2, in pullulanase sorting and secretion, the structural gene (pulA) was subjected to site-directed mutagenesis. Replacement of the Asp2 residue by Asn, Glu, or Ser caused the enzyme to fractionate with outer membrane-derived vesicles rather than with intermediate density vesicles from E. coli cells devoid of pullulanase secretion genes. A pronounced secretion defect was observed in a two-step secretion assay in which the first (sec gene-dependent) and second (pul gene-dependent) secretion steps were uncoupled. We propose that the Asp residue increases the efficiency of pullulanase secretion by allowing the enzyme to be initially sorted to a region of the cell envelope wherein most of the pullulase-specific secretion factors are located.

Regulation of hepatic high density lipoprotein binding proteins after administration of simvastatin and cholestyramine to rats.

We investigated the regulation of putative high density lipoprotein (HDL) receptors in rat liver after cholesterol feeding and the administration of cholesterol-lowering drugs to rats. The expression of two plasma membrane HDL binding proteins (HB1 and HB2) were compared in control and treated livers by first separating membrane proteins on sodium dodecyl sulfate-polyacrylamide gels and quantitating HB1 and HB2 levels with a specific ligand blot assay. Of the various treatments used, only simvastatin or simvastatin plus cholestyramine produced significant changes, with reductions of up to 40% and 60%, respectively, for HB1 and HB2. The effect on the binding proteins was not associated with changes in serum cholesterol concentrations, which did not change significantly after either treatment, although a marked rise in liver cholesterol concentration after cholesterol was associated with a moderate increase in HB2 expression. We show evidence for regulation of the levels of hepatic HDL binding proteins and provide another important criterion for the acceptance of HB1 and HB2 as components of a functional HDL receptor.

Purification of a putative lipoprotein receptor from Schistosoma japonicum adult worms

A 43-kDa putative lipoprotein receptor from Schistosoma japonicum adult worms (Sj43) has been purified by reverse-phase high-performance liquid chromatography (HPLC) using a Waters Delta-pak C4 300 Å 15 μ 3.9 mm × 300 mm column. A linear acetonitrile gradient from 10–95%, spanning 40 min and at a flow rate of 0.9 ml min −1 was employed for the elution of bound material. Sj43 had a retention time of approximately 13 min on the column, whereas other main components from the parasite extract had a much longer retention time. Sj43 purified as a doublet which could be cleaved with Staphylococcus aureus V8 protease but was unaffected by treatment with a mixture of endoglycosidase F and glycopeptidase F. Human low-density lipoprotein exhibited typical saturation kinetics on the HPLC-purified Sj43 with a calculated stoichiometry of 2 mol LDL mol −1 of the putative receptor. No evidence of high-density lipoprotein (HDL3) saturation was observed on purified Sj43, this being of some interest since it parallels observations made with mammalian HDL3-binding proteins.

Sequence of the putative low-density lipoprotein receptor-binding regions of apolipoprotein B in mouse and hamster

The nucleotide sequences of 2.35 kb of the apoB genes (encoding apolipoprotein B) encompassing the low-density-lipoprotein receptor-binding domains from mouse and hamster, have been determined. The sequences are 87.6% identical at the DNA level and 84.6% identical at the protein level. The region is also highly conserved in pig and human.

Membrane topology of penicillin-binding protein 3 of Escherichia coli.

The beta-lactamase fusion vector, pJBS633, has been used to analyse the organization of penicillin-binding protein 3 (PBP3) in the cytoplasmic membrane of Escherichia coli. The fusion junctions in 84 in-frame fusions of the coding region of mature TEM beta-lactamase to random positions within the PBP3 gene were determined. Fusions of beta-lactamase to 61 different positions in PBP3 were obtained. Fusions to positions within the first 31 residues of PBP3 resulted in enzymatically active fusion proteins which could not protect single cells of E. coli from killing by ampicillin, indicating that the beta-lactamase moieties of these fusion proteins were not translocated to the periplasm. However, all fusions that contained greater than or equal to 36 residues of PBP3 provided single cells of E. coli with substantial levels of resistance to ampicillin, indicating that the beta-lactamase moieties of these fusion proteins were translocated to the periplasm. PBP3 therefore appeared to have a simple membrane topology with residues 36 to the carboxy-terminus exposed on the periplasmic side of the cytoplasmic membrane. This topology was confirmed by showing that PBP3 was protected from proteolytic digestion at the cytoplasmic side of the inner membrane but was completely digested by proteolytic attack from the periplasmic side. PBP3 was only inserted in the cytoplasmic membrane at its amino terminus since replacement of its putative lipoprotein signal peptide with a normal signal peptide resulted in a water-soluble, periplasmic form of the enzyme. The periplasmic form of PBP3 retained its penicillin-binding activity and appeared to be truly water-soluble since it fractionated, in the absence of detergents, with the expected molecular weight on Sephadex G-100 and was not retarded by hydrophobic interaction chromatography on Phenyl-Superose.

Identification of a multispecific lipoprotein receptor in adult Schistosoma japonicum by ligand blotting analyses

A 43-kDa putative lipoprotein receptor (Sj43) of adult Schistosoma japonicum worms has been identified using ligand blotting techniques. Single and two dimensional electrophoretic analyses showed that Sj43 consisted of a single acidic polypeptide with multiple lipoprotein specificity. The molecule bound 125I-labelled low-density (apo-B), very low-density or high-density (apo-A and/or apo-C) lipoproteins from different mammalian hosts that are permissive to S. japonicum infection, but did not bind mouse apo-A containing lipoprotein. The binding of 125I-labelled lipoprotein to Sj43 could be inhibited by unlabelled human LDL, EDTA or Suramin, or by chemical modification of lipoprotein lysine or arginine residues. Sj43 was localised at the parasite's tegument and gut lining.

Serum lipoprotein structure: resonance energy transfer localization of fluorescent lipid probes.

The location of several fluorescent chromophores in lipoproteins has been determined by using resonance energy transfer. The primary acceptor is 5-(N-hexadecanoylamino)fluorescein whose chromophore is shown to reside at the lipoprotein surface at pH 7.4. Polar donors include cis-parinaric acid (cis,trans,trans,cis-9,11,13,15-octadecatetraenoic acid), trans-parinaric acid (all-trans-9,11,13,15-octadecatetraenoic acid), and 16-(9-anthroyloxy)palmitic acid; nonpolar donors are parinaric acid methyl ester, parinaric acid cholesteryl ester, and 1,6-diphenyl-1,3,5-hexatriene. The polar donors transfer more efficiently than the nonpolar donors in several classes of lipoprotein particles. The data are analyzed by a simple mathematical model from which it is concluded that the polar donors are localized in the putative lipoprotein surface monolayer; the possibility that nonpolar donors are partitioned between the surface and core of lipoproteins is considered.