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FEBS Letters Jul 2007ATP synthase, or F-ATPase, purified from bovine heart mitochondria in the absence of phospholipids is an assembly of 16 different subunits. In the presence of exogenous...
ATP synthase, or F-ATPase, purified from bovine heart mitochondria in the absence of phospholipids is an assembly of 16 different subunits. In the presence of exogenous phospholipids, two additional hydrophobic proteins, a 6.8kDa proteolipid and diabetes associated protein in insulin sensitive tissue (DAPIT), were associated with the purified complex, with DAPIT at sub-stoichiometric levels. Both proteins are conserved in vertebrates and invertebrates, but not in fungi, and prokaryotic F-ATPases do not contain orthologues of either of them. Therefore, their roles are likely to be peripheral to the synthesis of ATP.
Topics: Animals; Cattle; Membrane Proteins; Mitochondria, Heart; Mitochondrial Proton-Translocating ATPases; Protein Binding; Proteolipids
PubMed: 17570365
DOI: 10.1016/j.febslet.2007.05.079 -
Biology of the Neonate Sep 1998Surfactant preparations for the treatment of respiratory distress syndrome (RDS) that contain phospholipids and small amounts of the two hydrophobic proteins, SP-B and... (Review)
Review
Surfactant preparations for the treatment of respiratory distress syndrome (RDS) that contain phospholipids and small amounts of the two hydrophobic proteins, SP-B and SP-C, are presently obtained from animal lungs. Since structural information about SP-B and SP-C is available, it appears possible to design analogues that can replace the native proteins in synthetic surfactants. SP-C contains a single helix, but analogues with the poly-Val sequence of the native molecule do not fold into a native-like alpha-helical conformation. However, replacement of all Val with Leu yields efficient folding into a helical structure and Leu-based SP-C analogues effectively accelerate spreading of surfactant lipids and exhibit some physiological activity in animal models of RDS. The inferior in vivo activity of synthetic surfactants containing SP-C only compared to that of surfactant preparations derived from natural sources may be caused by a lack of covalently linked palmitoyl groups in the analogues and/or absence of SP-B. SP-B is significantly larger than SP-C and has a tertiary fold of several amphipathic helices in a dimeric structure. A single simplified amphipathic helical peptide containing only Leu and Lys does not mimic the surface properties of SP-B in vitro. These circumstances make the design of SP-B analogues from solely structural considerations less likely to be successful than in the case of SP-C.
Topics: Drug Design; Humans; Infant, Newborn; Infant, Premature; Proteolipids; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 9730586
DOI: 10.1159/000047029 -
Molecular Genetics and Metabolism 2000Mammalian lung surfactant is a mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C, and SP-D). Its major function is to reduce surface... (Review)
Review
Mammalian lung surfactant is a mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C, and SP-D). Its major function is to reduce surface tension at the air-water interface in the terminal airways by the formation of a surface-active film highly enriched in dipalmitoyl phosphatidylcholine (DPPC), thereby preventing alveolar collapse during expiration. SP-A and SP-D are large hydrophilic proteins, which play an important role in host defense, whereas the small hydrophobic peptides SP-B and SP-C interact with DPPC to generate and maintain a surface-active film. Surfactant replacement therapy with bovine and porcine lung surfactant extracts, which contain only polar lipids and SP-B and SP-C, has revolutionized the clinical management of premature infants with respiratory distress syndrome. Newer surfactant preparations will probably be based on SP-B and SP-C, produced by recombinant technology or peptide synthesis, and reconstituted with selected synthetic lipids. The development of peptide analogues of SP-B and SP-C offers the possibility to study their molecular mechanism of action and will allow the design of surfactant formulations for specific pulmonary diseases and better quality control. This review describes the hydrophobic peptide analogues developed thus far and their potential for use in a new generation of synthetic surfactant preparations.
Topics: Amino Acid Sequence; Animals; Cattle; Drug Design; Humans; Infant, Newborn; Models, Molecular; Molecular Sequence Data; Proteolipids; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 11001826
DOI: 10.1006/mgme.2000.3053 -
The Journal of Investigative Dermatology Feb 1988Since the first description of organic-soluble proteins (i.e., proteolipids), much attention has focused on the isolation, purification, characterization, localization,...
Since the first description of organic-soluble proteins (i.e., proteolipids), much attention has focused on the isolation, purification, characterization, localization, and function of these intrinsic membrane proteins in a variety of different tissues. Using a rapid purification scheme, which allowed the transfer of organic-soluble proteolipids to aqueous phases, we have isolated proteolipids from cultured human keratinocytes and human epidermis for the first time. A partial characterization of these proteolipids, including molecular-weight determination by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), amino acid composition, and an N-terminal sequencing revealed a preponderance of hydrophobic amino acids (greater than 60% overall and greater than 78% in N-terminal sequence), typical of other proteolipids. The composition of fatty acids, covalently bound to whole purified apoprotein fractions, displayed a predominance of palmitic greater than oleic greater than stearic acids. Comparison of the molecular species of proteolipids isolated from whole epidermis with those obtained from keratinocyte cultures by SDS-PAGE revealed a comparable spectrum of apoprotein species. Finally, subcellular fractionation of cultured keratinocytes, used to localize proteolipids to specific cellular compartments, suggested that one of the major apoprotein species (30 kD) is present in mitochondria, whereas the lower molecular weight species are localized in plasma membrane-enriched fractions. Although evidence is lacking for a specific function(s) of this class of molecules in the epidermis, the hypothesis that it plays a role in epidermal differentiation, for example, as constituents of calcium and/or proton pumps, is discussed.
Topics: Amino Acids; Apoproteins; Calcium; Chromatography, Thin Layer; Electrophoresis, Polyacrylamide Gel; Epidermis; Humans; Keratins; Molecular Weight; Proteolipids; Protons
PubMed: 2448390
DOI: 10.1111/1523-1747.ep12462203 -
Journal of Neuroscience Research Dec 1997The past few years have seen a dramatic increase in our understanding, in molecular terms, of the involvement of the central nervous system proteolipid protein in... (Review)
Review
The past few years have seen a dramatic increase in our understanding, in molecular terms, of the involvement of the central nervous system proteolipid protein in myelinogenesis and X-linked genetic diseases. In addition, we have expanded our knowledge of the proteins that have been recruited into the vertebrate myelin membrane over the past 400 million years with the molecular cloning of several cDNAs encoding proteins which are homologous to the proteolipid protein gene. In searching for a name to distinguish these proteins from other "proteolipid" proteins of nonneural origin I propose that we resurrect the term "lipophilins" which describes a small family of unusually hydrophobic integral membrane proteins exhibiting identical topologies and similar physical properties. Two subgroups are distinguishable among the lipophilins based on the patterns of expression during development and the presence or absence of a small motif that is exposed to the extracellular space.
Topics: Amino Acid Sequence; Animals; Conserved Sequence; Models, Molecular; Molecular Sequence Data; Myelin Proteins; Phylogeny; Protein Conformation; Proteolipids; Secretoglobins; Sequence Alignment; Sequence Homology, Amino Acid; Uteroglobin; Vertebrates
PubMed: 9418954
DOI: 10.1002/(SICI)1097-4547(19971201)50:5<659::AID-JNR3>3.0.CO;2-G -
Infection and Immunity Sep 1989A number of the major pathogen-specific immunogens of Treponema pallidum were characterized recently as amphiphilic, integral membrane proteins by phase partitioning...
A number of the major pathogen-specific immunogens of Treponema pallidum were characterized recently as amphiphilic, integral membrane proteins by phase partitioning with Triton X-114 (J. D. Radolf, N. R. Chamberlain, A. Clausell, and M. V. Norgard. Infect. Immun. 56:490-498, 1988). In the present study, we demonstrated that the same membrane immunogens (designated as detergent phase proteins [DPPs]) become radiolabeled upon in vitro incubation of T. pallidum with various 3H-labeled fatty acids. Radioimmunoprecipitation with a monoclonal antibody confirmed that the 3H-labeled 47-kilodalton protein corresponded to the well-characterized treponemal antigen with the identical apparent molecular mass. Failure to detect 3H-labeled DPPs following incubation with erythromycin confirmed that protein acylation required de novo protein synthesis by the bacteria. When treponemes were incubated with [3H]myristate, [3H]palmitate, or [3H]oleate, radiolabeled proteins corresponding to the DPPs were detected upon autoradiography. Demonstration that a number of the abundant membrane immunogens of T. pallidum are proteolipids provides information to help clarify their membrane association(s) and may serve to explain their extraordinary immunogenicity.
Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Fatty Acids; Membrane Proteins; Proteolipids; Rabbits; Structure-Activity Relationship; Treponema pallidum; Tritium
PubMed: 2668191
DOI: 10.1128/iai.57.9.2872-2877.1989 -
Plant Physiology Apr 2020Plasma membranes provide a highly selective environment for a large number of transmembrane and membrane-associated proteins. Whereas lateral movement of proteins in... (Review)
Review
Plasma membranes provide a highly selective environment for a large number of transmembrane and membrane-associated proteins. Whereas lateral movement of proteins in this lipid bilayer is possible, it is rather limited in turgid and cell wall-shielded plant cells. However, membrane-resident signaling processes occur on subsecond scales that cannot be explained by simple diffusion models. Accordingly, several receptors and other membrane-associated proteins are organized and functional in membrane nanodomains. Although the general presence of membrane nanodomains has become widely accepted as fact, fundamental functional aspects, the roles of individual lipid species and their interplay with proteins, and aspects of nanodomain maintenance and persistence remain poorly understood. Here, we review the current knowledge of nanodomain organization and function, with a particular focus on signaling processes involving proteins, lipids, and their interactions. Furthermore, we propose new and hypothetical aspects of plant membrane biology that we consider important for future research.
Topics: Cell Membrane; Membrane Microdomains; Models, Biological; Proteolipids; Signal Transduction
PubMed: 31857424
DOI: 10.1104/pp.19.01349 -
Journal of Neurochemistry May 2002In this study, we have investigated the structure of the native myelin proteolipid protein (PLP), DM-20 protein and several low molecular mass proteolipids by mass...
In this study, we have investigated the structure of the native myelin proteolipid protein (PLP), DM-20 protein and several low molecular mass proteolipids by mass spectrometry. The various proteolipid species were isolated from bovine spinal cord by size-exclusion and ion-exchange chromatography in organic solvents. Matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) of PLP and DM-20 revealed molecular masses of 31.6 and 27.2 kDa, respectively, which is consistent with the presence of six and four molecules of thioester-bound fatty acids. Electrospray ionization-MS analysis of the deacylated proteins in organic solvents produced the predicted molecular masses of the apoproteins (29.9 and 26.1 kDa), demonstrating that palmitoylation is the major post-translational modification of PLP, and that the majority of PLP and DM-20 molecules in the CNS are fully acylated. A series of myelin-associated, palmitoylated proteolipids with molecular masses raging between 12 kDa and 18 kDa were also isolated and subjected to amino acid analysis, fatty acid analysis, N- and C-terminal sequencing, tryptic digestion and peptide mapping by MALDI-TOF-MS. The results clearly showed that these polypeptides correspond to the N-terminal region (residues 1-105/112) and C-terminal region (residues 113/131-276) of the major PLP, and they appear to be produced by natural proteolytic cleavage within the 60 amino acid-long cytoplasmic domain. These proteolipids are not postmortem artifacts of PLP and DM-20, and are differentially distributed across the CNS.
Topics: Acylation; Amino Acids; Animals; Cattle; Chromatography, Gel; Chromatography, Ion Exchange; Fatty Acids; Membrane Proteins; Molecular Weight; Myelin Proteolipid Protein; Palmitic Acids; Peptide Fragments; Proteolipids; Solvents; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spinal Cord
PubMed: 12065672
DOI: 10.1046/j.1471-4159.2002.00852.x -
Annual Review of Physiology 2001SP-B is the only surfactant-associated protein absolutely required for postnatal lung function and survival. Complete deficiency of SP-B in mice and humans results in... (Review)
Review
SP-B is the only surfactant-associated protein absolutely required for postnatal lung function and survival. Complete deficiency of SP-B in mice and humans results in lethal, neonatal respiratory distress syndrome and is characterized by a virtual absence of lung compliance, highly disorganized lamellar bodies, and greatly diminished levels of SP-C mature peptide; in contrast, lung structure and function in SP-C null mice is normal. This review attempts to integrate recent findings in humans and transgenic mice with the results of in vitro studies to provide a better understanding of the functions of SP-B and SP-C and the structural basis for their actions.
Topics: Amino Acid Sequence; Animals; Humans; Molecular Sequence Data; Proteolipids; Pulmonary Alveoli; Pulmonary Surfactants
PubMed: 11181967
DOI: 10.1146/annurev.physiol.63.1.555 -
General Pharmacology 1988
Review
Topics: Animals; Gene Expression Regulation; Humans; Molecular Weight; Proteolipids; Pulmonary Alveoli; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants
PubMed: 3046997
DOI: 10.1016/0306-3623(88)90029-8