Specific lipid requirements of membrane proteins--a putative bottleneck in heterologous expression.

Membrane proteins are mostly protein-lipid complexes. For more than 30 examples of membrane proteins from prokaryotes, yeast, plant and mammals, the importance of phospholipids and sterols for optimal activity is documented. All crystallized membrane protein complexes show defined lipid-protein contacts. In addition, lipid requirements may also be transitory and necessary only for correct folding and intercellular transport. With respect to specific lipid requirements of membrane proteins, the phospholipid and glycolipid as well as the sterol content of the host cell chosen for heterologous expression should be carefully considered. The lipid composition of bacteria, archaea, yeasts, insects,Xenopus oocytes, and typical plant and mammalian cells are given in this review. A few examples of heterologous expression of membrane proteins, where problems of specific lipid requirements have been noticed or should be thought of, have been chosen.

[1]  R. Nakamoto,et al.  Use of chemical chaperones in the yeast Saccharomyces cerevisiae to enhance heterologous membrane protein expression: high-yield expression and purification of human P-glycoprotein. , 2000, Archives of biochemistry and biophysics.

[2]  B. Hoffmann,et al.  The reconstituted ADP/ATP carrier activity has an absolute requirement for cardiolipin as shown in cysteine mutants. , 1994, The Journal of biological chemistry.

[3]  T. H. Wilson,et al.  Effect of different phospholipids on the reconstitution of two functions of the lactose carrier ofEscherichia coli , 2005, The Journal of Membrane Biology.

[4]  C. Tate,et al.  Overexpression of mammalian integral membrane proteins for structural studies , 2001, FEBS letters.

[5]  A. Bachhawat,et al.  The yeast multidrug resistance pump, Pdr5p, confers reduced drug resistance in erg mutants of Saccharomyces cerevisiae. , 1999, Microbiology.

[6]  M. Hartmann,et al.  Sterol Modulation of the Plasma Membrane H+-ATPase Activity from Corn Roots Reconstituted into Soybean Lipids , 1997, Plant physiology.

[7]  F. Sharom.  The P-glycoprotein multidrug transporter: interactions with membrane lipids, and their modulation of activity. , 1997, Biochemical Society transactions.

[8]  M. Bogdanov,et al.  Phospholipid‐assisted protein folding: phosphatidylethanolamine is required at a late step of the conformational maturation of the polytopic membrane protein lactose permease , 1998, The EMBO journal.

[9]  P. A. Pedersen,et al.  Expression in High Yield of Pig α1β1 Na,K-ATPase and Inactive Mutants D369N and D807N in Saccharomyces cerevisiae(*) , 1996, The Journal of Biological Chemistry.

[10]  R. Schneiter,et al.  Roles of phosphatidylethanolamine and of its several biosynthetic pathways in Saccharomyces cerevisiae. , 2001, Molecular biology of the cell.

[11]  J. Moore,et al.  Quantification of major classes of Xenopus phospholipids by high performance liquid chromatography with evaporative light scattering detection. , 2000, Journal of lipid research.

[12]  M. Bogdanov,et al.  A polytopic membrane protein displays a reversible topology dependent on membrane lipid composition , 2002, The EMBO journal.

[13]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[14]  A. Driessen,et al.  Bacterial solute transport proteins in their lipid environment. , 1993, FEMS microbiology reviews.

[15]  R. Cleland,et al.  Comparison of the lipid composition of oat root and coleoptile plasma membranes: lack of short-term change in response to auxin. , 1989, Plant physiology.

[16]  Christoph Benning,et al.  Arabidopsis disrupted in SQD2 encoding sulfolipid synthase is impaired in phosphate-limited growth , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Santiago,et al.  Probing the Effects of Membrane Cholesterol in the Torpedo californica Acetylcholine Receptor and the Novel Lipid-exposed Mutation αC418W in XenopusOocytes* , 2001, The Journal of Biological Chemistry.

[18]  D. Williams,et al.  Membrane cholesterol modulates serotonin transporter activity. , 2001, Biochemistry.

[19]  K. Karlsson.  Animal glycosphingolipids as membrane attachment sites for bacteria. , 1989, Annual review of biochemistry.

[20]  H. Kolbe,et al.  The mitochondrial phosphate carrier has an essential requirement for cardiolipin , 1982, FEBS letters.

[21]  N. C. Robinson,et al.  Specificity and binding affinity of phospholipids to the high-affinity cardiolipin sites of beef heart cytochrome c oxidase. , 1982, Biochemistry.

[22]  G. Gimpl,et al.  Regulation of receptor function by cholesterol , 2000, Cellular and Molecular Life Sciences CMLS.

[23]  K. Matsumoto,et al.  Dispensable nature of phosphatidylglycerol in Escherichia coli: dual roles of anionic phospholipids , 2001, Molecular microbiology.

[24]  T. Caspari,et al.  Functional expression of the Chlorella hexose transporter in Schizosaccharomyces pombe. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[25]  D. Allan.  Mapping the lipid distribution in the membranes of BHK cells (mini-review). , 1996, Molecular membrane biology.

[26]  C. Benning,et al.  Galactolipids rule in seed plants. , 2002, Trends in plant science.

[27]  D. Voelker,et al.  Phosphatidylserine Decarboxylase 2 of Saccharomyces cerevisiáe , 1995, The Journal of Biological Chemistry.

[28]  B. Trumpower,et al.  Specific roles of protein–phospholipid interactions in the yeast cytochrome bc1 complex structure , 2001, The EMBO journal.

[29]  E. Morris,et al.  Phosphatidylglycerol Is Involved in the Dimerization of Photosystem II* , 2000, The Journal of Biological Chemistry.

[30]  F. Sharom,et al.  The membrane lipid environment modulates drug interactions with the P-glycoprotein multidrug transporter. , 1999, Biochemistry.

[31]  F. L. Crane,et al.  Tightly bound cardiolipin in cytochrome oxidase. , 1971, Biochimica et biophysica acta.

[32]  B. Kammerer,et al.  Expression of the functional mature chloroplast triose phosphate translocator in yeast internal membranes and purification of the histidine-tagged protein by a single metal-affinity chromatography step. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[33]  H. Michel,et al.  Expression of the human D2S dopamine receptor in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe: A comparative study , 1994, FEBS letters.

[34]  C. Gahmberg,et al.  The lipids of the plasma membranes and endoplasmic reticulum from cultured baby hamster kidney cells (BHK21). , 1972, Biochimica et biophysica acta.

[35]  P. Cronet,et al.  Functional reconstitution of purified metabotropic glutamate receptor expressed in the fly eye , 2002, EMBO reports.

[36]  J. González-Ros,et al.  A role for cholesterol as a structural effector of the nicotinic acetylcholine receptor. , 1994, Biochemistry.

[37]  K. Simons,et al.  Plasma membrane proton ATPase Pma1p requires raft association for surface delivery in yeast. , 2001, Molecular biology of the cell.

[38]  W. Kühlbrandt,et al.  Lipid-protein interactions in crystals of plant light-harvesting complex. , 1993, Journal of molecular biology.

[39]  P. Gros,et al.  Functional expression of mouse mdr1 in Escherichia coli. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[40]  D. Schachtman,et al.  Identification and characterization of plant transporters , 1999 .

[41]  R. Hendler,et al.  Importance of specific native lipids in controlling the photocycle of bacteriorhodopsin. , 1998, Biochemistry.

[42]  R. Lester,et al.  The phosphoinositol sphingolipids of Saccharomyces cerevisiae are highly localized in the plasma membrane , 1991, Journal of bacteriology.

[43]  W. Lehmann,et al.  Lipid patches in membrane protein oligomers: crystal structure of the bacteriorhodopsin-lipid complex. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[44]  H Luecke,et al.  Structure of bacteriorhodopsin at 1.55 A resolution. , 1999, Journal of molecular biology.

[45]  K. Beyer,et al.  Specific cardiolipin binding interferes with labeling of sulfhydryl residues in the adenosine diphosphate/adenosine triphosphate carrier protein from beef heart mitochondria. , 1996, Biochemistry.

[46]  G. Gimpl,et al.  Alteration of the myometrial plasma membrane cholesterol content with beta-cyclodextrin modulates the binding affinity of the oxytocin receptor. , 1995, Biochemistry.

[47]  J. Masson,et al.  Role of Sterols in Modulating the Human μ-Opioid Receptor Function in Saccharomyces cerevisiae * , 2000, The Journal of Biological Chemistry.

[48]  B. Baggenstoss,et al.  Purification and Lipid Dependence of the Recombinant Hyaluronan Synthases from Streptococcus pyogenes andStreptococcus equisimilis * , 1999, The Journal of Biological Chemistry.

[49]  T. Caspari,et al.  Purification of the Chlorella HUP1 hexose-proton symporter to homogeneity and its reconstitution in vitro. , 1996, The Plant journal : for cell and molecular biology.

[50]  M. Palmgren,et al.  Purification of a histidine-tagged plant plasma membrane H+-ATPase expressed in yeast. , 1998, Protein expression and purification.

[51]  G. A. Scarborough,et al.  Purification of functional human P-glycoprotein expressed in Saccharomyces cerevisiae. , 1997, Biochimica et biophysica acta.

[52]  N. Sato,et al.  Direct evidence for requirement of phosphatidylglycerol in photosystem II of photosynthesis. , 2000, Plant physiology.

[53]  L. W. Parks,et al.  Multiple functions for sterols in Saccharomyces cerevisiae. , 1985, Biochimica et biophysica acta.

[54]  B. Poolman,et al.  On the osmotic signal and osmosensing mechanism of an ABC transport system for glycine betaine , 2001, The EMBO journal.

[55]  P. Gros,et al.  Functional expression of multidrug resistance protein 1 in Pichia pastoris. , 2001, Biochemistry.

[56]  M. Saraste,et al.  FEBS Lett , 2000 .

[57]  W. Dowhan.  Genetic analysis of lipid-protein interactions in Escherichia coli membranes. , 1998, Biochimica et biophysica acta.

[58]  D. Langosch,et al.  Strategies for Prokaryotic Expression of Eukaryotic Membrane Proteins , 2001, Traffic.

[59]  P. Wrede,et al.  Genetic transfer of the pigment bacteriorhodopsin into the eukaryote Schizosaccharomyces pombe , 1989, FEBS letters.

[60]  R. Grisshammer,et al.  Purification and characterization of the human adenosine A2a receptor functionally expressed in Escherichia coli , 2002 .

[61]  H Breer,et al.  Expression of an olfactory receptor in Escherichia coli: purification, reconstitution, and ligand binding. , 1996, Biochemistry.

[62]  Petra Fromme,et al.  Three-dimensional structure of cyanobacterial photosystem I at 2.5 Å resolution , 2001, Nature.

[63]  Miss A.O. Penney.  (b) , 1974, The New Yale Book of Quotations.

[64]  A. Rietveld,et al.  Non‐bilayer lipids are required for efficient protein transport across the plasma membrane of Escherichia coli. , 1995, The EMBO journal.

[65]  T. Caspari,et al.  MEMBRANE TRANSPORT CARRIERS. , 1996, Annual review of plant physiology and plant molecular biology.

[66]  J. East,et al.  Binding sites for cholesterol on Ca(2+)-ATPase studied by using a cholesterol-containing phospholipid. , 1994, Biochemistry.

[67]  M. Graziano,et al.  Membrane cholesterol modulates galanin-GalR2 interaction. , 1999, Biochemistry.

[68]  W. Tanner,et al.  Nystatin changes the properties of transporters for arginine and sugars An in vitro study , 1994, FEBS letters.

[69]  A. Azzi,et al.  The monocarboxylate carrier from bovine heart mitochondria: partial purification and its substrate-transporting properties in a reconstituted system. , 1986, Biochimica et biophysica acta.

[70]  C. Tate,et al.  Overexpression of integral membrane proteins for structural studies , 1995, Quarterly Reviews of Biophysics.

[71]  M. Bogdanov,et al.  Phosphatidylethanolamine Is Required for in Vivo Function of the Membrane-associated Lactose Permease of Escherichia coli(*) , 1995, The Journal of Biological Chemistry.

[72]  B. Kruijff,et al.  Topology and transport of membrane lipids in bacteria. , 2000, Biochimica et biophysica acta.

[73]  B. Kanner,et al.  Cholesterol is required for the reconstruction of the sodium- and chloride-coupled, gamma-aminobutyric acid transporter from rat brain. , 1990, The Journal of biological chemistry.

[74]  K. Marheineke,et al.  Lipid composition of Spodoptera frugiperda (Sf9) and Trichoplusia ni (Tn) insect cells used for baculovirus infection , 1998, FEBS letters.

[75]  J. Tucker,et al.  Purification of a rat neurotensin receptor expressed in Escherichia coli. , 1996, The Biochemical journal.

[76]  R. Epand,et al.  Effect of cholesterol on rhodopsin stability in disk membranes. , 1996, Biochimica et biophysica acta.

[77]  S. Negash,et al.  Phosphatidylethanolamine modulates Ca-ATPase function and dynamics. , 1999, Biochemistry.

[78]  M. Overduin,et al.  Phosphatidylethanolamine Has an Essential Role inSaccharomyces cerevisiae That Is Independent of Its Ability to Form Hexagonal Phase Structures* , 2001, The Journal of Biological Chemistry.

[79]  R. Serrano,et al.  Lipid requirements of the plasma membrane ATPases from oat roots and yeast , 1988 .

[80]  E. Ikonen,et al.  Functional rafts in cell membranes , 1997, Nature.

[81]  F. Cornelius.  Modulation of Na,K-ATPase and Na-ATPase activity by phospholipids and cholesterol. I. Steady-state kinetics. , 2001, Biochemistry.

[82]  W. Tanner,et al.  Construction of phosphatidylethanolamine‐less strain of Saccharomyces cerevisiae. Effect on amino acid transport , 2001, Yeast.

[83]  B. Kruijff.  Lipid polymorphism and biomembrane function , 1997 .

[84]  C. Higgins,et al.  The importance of cholesterol in maintenance of P-glycoprotein activity and its membrane perturbing influence , 2001, European Biophysics Journal.

[85]  C. Y. Chen,et al.  Synthesis and assembly of functional mammalian Na,K-ATPase in yeast. , 1990, The Journal of biological chemistry.

[86]  D. Kelly,et al.  Systematic analysis of yeast strains with possible defects in lipid metabolism , 1999, Yeast.

[87]  K. Ueda,et al.  Functional expression of human P‐glycoprotein in Schizosaccharomyces pombe , 1993, FEBS letters.

[88]  B. de Kruijff,et al.  Anionic phospholipids are involved in membrane association of FtsY and stimulate its GTPase activity , 2000, The EMBO journal.

[89]  M. Varsanyi,et al.  Activation of sarcoplasmic reticular Ca2+ transport ATPase by phosphorylation of an associated phosphatidylinositol. , 1983, The EMBO journal.

[90]  N. Sauer,et al.  Functional reconstitution of the solubilized Arabidopsis thaliana STP1 monosaccharide-H+ symporter in lipid vesicles and purification of the histidine tagged protein from transgenic Saccharomyces cerevisiae. , 1994, The Plant journal : for cell and molecular biology.

[91]  L. Li,et al.  Sequence properties of the 1,2-diacylglycerol 3-glucosyltransferase from Acholeplasma laidlawii membranes. Recognition of a large group of lipid glycosyltransferases in eubacteria and archaea. , 2001, The Journal of biological chemistry.

[92]  T. Wilson,et al.  The phospholipid requirement for activity of the lactose carrier of Escherichia coli. , 1984, The Journal of biological chemistry.

[93]  K. Boesze-Battaglia,et al.  Cell membrane lipid composition and distribution: implications for cell function and lessons learned from photoreceptors and platelets. , 1997, The Journal of experimental biology.

[94]  W. H. Evans,et al.  The lipid composition of plasma membrane subfractions originating from the three major functional domains of the rat hepatocyte cell surface. , 1976, Biochimica et biophysica acta.

[95]  G. Gimpl,et al.  Expression of the human oxytocin receptor in baculovirus-infected insect cells: high-affinity binding is induced by a cholesterol-cyclodextrin complex. , 1995, Biochemistry.

[96]  A. Driessen,et al.  Non-bilayer Lipids Stimulate the Activity of the Reconstituted Bacterial Protein Translocase* , 2000, The Journal of Biological Chemistry.

[97]  A. Ohta,et al.  Phosphatidylserine Synthesis Required for the Maximal Tryptophan Transport Activity in Saccharomyces cerevisiae , 2000, Bioscience, biotechnology, and biochemistry.

[98]  M. Runswick,et al.  Characterisation of new intracellular membranes in Escherichia coli accompanying large scale over‐production of the b subunit of F1Fo ATP synthase , 2000, FEBS letters.

[99]  E. Cabib,et al.  Solubilization and partial purification of yeast chitin synthetase. Confirmation of the zymogenic nature of the enzyme. , 1978, The Journal of biological chemistry.

[100]  W. Dowhan,et al.  Molecular basis for membrane phospholipid diversity: why are there so many lipids? , 1997, Annual review of biochemistry.

[101]  A. Winter-Vann,et al.  Heterologous gene expression in a membrane-protein-specific system. , 1999, Protein expression and purification.

[102]  G. Lindblom,et al.  Wild-type Escherichia coli Cells Regulate the Membrane Lipid Composition in a Window between Gel and Non-lamellar Structures (*) , 1996, The Journal of Biological Chemistry.

[103]  N. C. Robinson,et al.  Cardiolipin-depleted bovine heart cytochrome c oxidase: binding stoichiometry and affinity for cardiolipin derivatives. , 1990, Biochemistry.

[104]  R. MacKinnon,et al.  Chemistry of ion coordination and hydration revealed by a K+ channel–Fab complex at 2.0 Å resolution , 2001, Nature.

[105]  W. Tanner,et al.  Properties of a reconstituted eukaryotic hexose/proton symporter solubilized by structurally related non-ionic detergents: specific requirement of phosphatidylcholine for permease stability. , 2000, Biochimica et biophysica acta.

[106]  C Menzel,et al.  Protein, lipid and water organization in bacteriorhodopsin crystals: a molecular view of the purple membrane at 1.9 A resolution. , 1999, Structure.

[107]  W. Knogge,et al.  Sterol glycosides and cerebrosides accumulate in Pichia pastoris, Rhynchosporium secalis and other fungi under normal conditions or under heat shock and ethanol stress , 2001, Yeast.

[108]  W. Frommer.  Heterologous Expression of Genes in Bacterial, Fungal, Animal, and Plant Cells , 1995 .

[109]  W. Tanner,et al.  Expression of eukaryotic plasma membrane transporter HUP1 from Chlorella kessleri in Escherichia coli. , 1999, FEMS microbiology letters.

[110]  Anthony G. Lee,et al.  How lipids interact with an intrinsic membrane protein: the case of the calcium pump. , 1998, Biochimica et biophysica acta.

[111]  W. Tanner,et al.  Phosphatidyl ethanolamine is essential for targeting the arginine transporter Can1p to the plasma membrane of yeast. , 2002, Biochimica et Biophysica Acta.

[112]  M. Vidal,et al.  The yeast gene ERG6 is required for normal membrane function but is not essential for biosynthesis of the cell-cycle-sparking sterol , 1989, Molecular and cellular biology.

[113]  Hartmut Michel,et al.  Structure at 2.8 Å resolution of cytochrome c oxidase from Paracoccus denitrificans , 1995, Nature.

[114]  M R Jones,et al.  Structural details of an interaction between cardiolipin and an integral membrane protein. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[115]  M. Bogdanov,et al.  Lipid-assisted Protein Folding* , 1999, The Journal of Biological Chemistry.

[116]  S. Eaton,et al.  Association of Sterol- and Glycosylphosphatidylinositol-linked Proteins with Drosophila Raft Lipid Microdomains* , 1999, The Journal of Biological Chemistry.

[117]  J. Tommassen,et al.  Identification of phospholipids as new components that assist in the in vitro trimerization of a bacterial pore protein. , 2001, European journal of biochemistry.

[118]  J. Mulheron,et al.  Human 5-HT1A receptor expressed in insect cells activates endogenous G(o)-like G protein(s). , 1994, The Journal of biological chemistry.

[119]  M. L. Greenberg,et al.  The biosynthesis and functional role of cardiolipin. , 2000, Progress in lipid research.

[120]  G. Gimpl,et al.  Cholesterol as modulator of receptor function. , 1997, Biochemistry.

[121]  G. Daum,et al.  Isolation and biochemical characterization of organelles from the yeast, Saccharomyces cerevisiae , 1995, Yeast.