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. 1989 Aug;86(15):5786–5790. doi: 10.1073/pnas.86.15.5786

Predicting the orientation of eukaryotic membrane-spanning proteins.

E Hartmann 1, T A Rapoport 1, H F Lodish 1
PMCID: PMC297715  PMID: 2762295

Abstract

We have developed a rule to predict the orientation of the first internal signal-anchor sequence in eukaryotic transmembrane proteins synthesized on the rough endoplasmic reticulum. The difference in the charges of the 15 residues flanking the first internal signal-anchor determines its orientation, with the more positive portion facing the cytosol. In proteins that span the membrane more than once, the orientation of all subsequent transmembrane segments would be determined by that of the most N-terminal one.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alper S. L., Kopito R. R., Libresco S. M., Lodish H. F. Cloning and characterization of a murine band 3-related cDNA from kidney and from a lymphoid cell line. J Biol Chem. 1988 Nov 15;263(32):17092–17099. [PubMed] [Google Scholar]
  2. Beaune P. H., Umbenhauer D. R., Bork R. W., Lloyd R. S., Guengerich F. P. Isolation and sequence determination of a cDNA clone related to human cytochrome P-450 nifedipine oxidase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8064–8068. doi: 10.1073/pnas.83.21.8064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birnbaum M. J., Haspel H. C., Rosen O. M. Cloning and characterization of a cDNA encoding the rat brain glucose-transporter protein. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5784–5788. doi: 10.1073/pnas.83.16.5784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blobel G., Dobberstein B. Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J Cell Biol. 1975 Dec;67(3):835–851. doi: 10.1083/jcb.67.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blok J., Air G. M. Variation in the membrane-insertion and "stalk" sequences in eight subtypes of influenza type A virus neuraminidase. Biochemistry. 1982 Aug 17;21(17):4001–4007. doi: 10.1021/bi00260a015. [DOI] [PubMed] [Google Scholar]
  6. Bonner T. I., Buckley N. J., Young A. C., Brann M. R. Identification of a family of muscarinic acetylcholine receptor genes. Science. 1987 Jul 31;237(4814):527–532. doi: 10.1126/science.3037705. [DOI] [PubMed] [Google Scholar]
  7. Brown D. J., Hogue B. G., Nayak D. P. Redundancy of signal and anchor functions in the NH2-terminal uncharged region of influenza virus neuraminidase, a class II membrane glycoprotein. J Virol. 1988 Oct;62(10):3824–3831. doi: 10.1128/jvi.62.10.3824-3831.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Charron M. J., Brosius F. C., 3rd, Alper S. L., Lodish H. F. A glucose transport protein expressed predominately in insulin-responsive tissues. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2535–2539. doi: 10.1073/pnas.86.8.2535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chen C. J., Chin J. E., Ueda K., Clark D. P., Pastan I., Gottesman M. M., Roninson I. B. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell. 1986 Nov 7;47(3):381–389. doi: 10.1016/0092-8674(86)90595-7. [DOI] [PubMed] [Google Scholar]
  10. Date T., Goodman J. M., Wickner W. T. Procoat, the precursor of M13 coat protein, requires an electrochemical potential for membrane insertion. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4669–4673. doi: 10.1073/pnas.77.8.4669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Demuth D. R., Showe L. C., Ballantine M., Palumbo A., Fraser P. J., Cioe L., Rovera G., Curtis P. J. Cloning and structural characterization of a human non-erythroid band 3-like protein. EMBO J. 1986 Jun;5(6):1205–1214. doi: 10.1002/j.1460-2075.1986.tb04348.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Devault A., Lazure C., Nault C., Le Moual H., Seidah N. G., Chrétien M., Kahn P., Powell J., Mallet J., Beaumont A. Amino acid sequence of rabbit kidney neutral endopeptidase 24.11 (enkephalinase) deduced from a complementary DNA. EMBO J. 1987 May;6(5):1317–1322. doi: 10.1002/j.1460-2075.1987.tb02370.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dixon R. A., Kobilka B. K., Strader D. J., Benovic J. L., Dohlman H. G., Frielle T., Bolanowski M. A., Bennett C. D., Rands E., Diehl R. E. Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature. 1986 May 1;321(6065):75–79. doi: 10.1038/321075a0. [DOI] [PubMed] [Google Scholar]
  14. Drickamer K. Complete amino acid sequence of a membrane receptor for glycoproteins. Sequence of the chicken hepatic lectin. J Biol Chem. 1981 Jun 10;256(11):5827–5839. [PubMed] [Google Scholar]
  15. Drickamer K., Mamon J. F., Binns G., Leung J. O. Primary structure of the rat liver asialoglycoprotein receptor. Structural evidence for multiple polypeptide species. J Biol Chem. 1984 Jan 25;259(2):770–778. [PubMed] [Google Scholar]
  16. Eisenberg D., Schwarz E., Komaromy M., Wall R. Analysis of membrane and surface protein sequences with the hydrophobic moment plot. J Mol Biol. 1984 Oct 15;179(1):125–142. doi: 10.1016/0022-2836(84)90309-7. [DOI] [PubMed] [Google Scholar]
  17. Frielle T., Collins S., Daniel K. W., Caron M. G., Lefkowitz R. J., Kobilka B. K. Cloning of the cDNA for the human beta 1-adrenergic receptor. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7920–7924. doi: 10.1073/pnas.84.22.7920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fujii-Kuriyama Y., Mizukami Y., Kawajiri K., Sogawa K., Muramatsu M. Primary structure of a cytochrome P-450: coding nucleotide sequence of phenobarbital-inducible cytochrome P-450 cDNA from rat liver. Proc Natl Acad Sci U S A. 1982 May;79(9):2793–2797. doi: 10.1073/pnas.79.9.2793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gorin M. B., Yancey S. B., Cline J., Revel J. P., Horwitz J. The major intrinsic protein (MIP) of the bovine lens fiber membrane: characterization and structure based on cDNA cloning. Cell. 1984 Nov;39(1):49–59. doi: 10.1016/0092-8674(84)90190-9. [DOI] [PubMed] [Google Scholar]
  20. Haeuptle M. T., Flint N., Gough N. M., Dobberstein B. A tripartite structure of the signals that determine protein insertion into the endoplasmic reticulum membrane. J Cell Biol. 1989 Apr;108(4):1227–1236. doi: 10.1083/jcb.108.4.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hagen D. C., McCaffrey G., Sprague G. F., Jr Evidence the yeast STE3 gene encodes a receptor for the peptide pheromone a factor: gene sequence and implications for the structure of the presumed receptor. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1418–1422. doi: 10.1073/pnas.83.5.1418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. High S., Tanner M. J. Human erythrocyte membrane sialoglycoprotein beta. The cDNA sequence suggests the absence of a cleaved N-terminal signal sequence. Biochem J. 1987 Apr 1;243(1):277–280. doi: 10.1042/bj2430277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hull J. D., Gilmore R., Lamb R. A. Integration of a small integral membrane protein, M2, of influenza virus into the endoplasmic reticulum: analysis of the internal signal-anchor domain of a protein with an ectoplasmic NH2 terminus. J Cell Biol. 1988 May;106(5):1489–1498. doi: 10.1083/jcb.106.5.1489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hunziker W., Spiess M., Semenza G., Lodish H. F. The sucrase-isomaltase complex: primary structure, membrane-orientation, and evolution of a stalked, intrinsic brush border protein. Cell. 1986 Jul 18;46(2):227–234. doi: 10.1016/0092-8674(86)90739-7. [DOI] [PubMed] [Google Scholar]
  25. Ikuta K., Takami M., Kim C. W., Honjo T., Miyoshi T., Tagaya Y., Kawabe T., Yodoi J. Human lymphocyte Fc receptor for IgE: sequence homology of its cloned cDNA with animal lectins. Proc Natl Acad Sci U S A. 1987 Feb;84(3):819–823. doi: 10.1073/pnas.84.3.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Inouye M., Halegoua S. Secretion and membrane localization of proteins in Escherichia coli. CRC Crit Rev Biochem. 1980;7(4):339–371. doi: 10.3109/10409238009105465. [DOI] [PubMed] [Google Scholar]
  27. Julius D., MacDermott A. B., Axel R., Jessell T. M. Molecular characterization of a functional cDNA encoding the serotonin 1c receptor. Science. 1988 Jul 29;241(4865):558–564. doi: 10.1126/science.3399891. [DOI] [PubMed] [Google Scholar]
  28. Kagawa N., Mihara K., Sato R. Structural analysis of cloned cDNAs for polycyclic hydrocarbon-inducible forms of rabbit liver microsomal cytochrome P-450. J Biochem. 1987 Jun;101(6):1471–1479. doi: 10.1093/oxfordjournals.jbchem.a122017. [DOI] [PubMed] [Google Scholar]
  29. Katagiri M., Murakami H., Yabusaki Y., Sugiyama T., Okamoto M., Yamano T., Ohkawa H. Molecular cloning and sequence analysis of full-length cDNA for rabbit liver NADPH-cytochrome P-450 reductase mRNA. J Biochem. 1986 Oct;100(4):945–954. doi: 10.1093/oxfordjournals.jbchem.a121807. [DOI] [PubMed] [Google Scholar]
  30. Kayano T., Noda M., Flockerzi V., Takahashi H., Numa S. Primary structure of rat brain sodium channel III deduced from the cDNA sequence. FEBS Lett. 1988 Feb 8;228(1):187–194. doi: 10.1016/0014-5793(88)80614-8. [DOI] [PubMed] [Google Scholar]
  31. Klein P., Kanehisa M., DeLisi C. The detection and classification of membrane-spanning proteins. Biochim Biophys Acta. 1985 May 28;815(3):468–476. doi: 10.1016/0005-2736(85)90375-x. [DOI] [PubMed] [Google Scholar]
  32. Kobilka B. K., Matsui H., Kobilka T. S., Yang-Feng T. L., Francke U., Caron M. G., Lefkowitz R. J., Regan J. W. Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science. 1987 Oct 30;238(4827):650–656. doi: 10.1126/science.2823383. [DOI] [PubMed] [Google Scholar]
  33. Kopito R. R., Lodish H. F. Primary structure and transmembrane orientation of the murine anion exchange protein. Nature. 1985 Jul 18;316(6025):234–238. doi: 10.1038/316234a0. [DOI] [PubMed] [Google Scholar]
  34. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  35. Lamb R. A., Zebedee S. L., Richardson C. D. Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface. Cell. 1985 Mar;40(3):627–633. doi: 10.1016/0092-8674(85)90211-9. [DOI] [PubMed] [Google Scholar]
  36. Laperche Y., Bulle F., Aissani T., Chobert M. N., Aggerbeck M., Hanoune J., Guellaën G. Molecular cloning and nucleotide sequence of rat kidney gamma-glutamyl transpeptidase cDNA. Proc Natl Acad Sci U S A. 1986 Feb;83(4):937–941. doi: 10.1073/pnas.83.4.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Li P., Beckwith J., Inouye H. Alteration of the amino terminus of the mature sequence of a periplasmic protein can severely affect protein export in Escherichia coli. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7685–7689. doi: 10.1073/pnas.85.20.7685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lipp J., Dobberstein B. The membrane-spanning segment of invariant chain (I gamma) contains a potentially cleavable signal sequence. Cell. 1986 Sep 26;46(7):1103–1112. doi: 10.1016/0092-8674(86)90710-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Machamer C. E., Rose J. K. A specific transmembrane domain of a coronavirus E1 glycoprotein is required for its retention in the Golgi region. J Cell Biol. 1987 Sep;105(3):1205–1214. doi: 10.1083/jcb.105.3.1205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Malfroy B., Kuang W. J., Seeburg P. H., Mason A. J., Schofield P. R. Molecular cloning and amino acid sequence of human enkephalinase (neutral endopeptidase). FEBS Lett. 1988 Feb 29;229(1):206–210. doi: 10.1016/0014-5793(88)80828-7. [DOI] [PubMed] [Google Scholar]
  41. Masu Y., Nakayama K., Tamaki H., Harada Y., Kuno M., Nakanishi S. cDNA cloning of bovine substance-K receptor through oocyte expression system. 1987 Oct 29-Nov 4Nature. 329(6142):836–838. doi: 10.1038/329836a0. [DOI] [PubMed] [Google Scholar]
  42. Mohana Rao J. K., Argos P. A conformational preference parameter to predict helices in integral membrane proteins. Biochim Biophys Acta. 1986 Jan 30;869(2):197–214. doi: 10.1016/0167-4838(86)90295-5. [DOI] [PubMed] [Google Scholar]
  43. Monier S., Van Luc P., Kreibich G., Sabatini D. D., Adesnik M. Signals for the incorporation and orientation of cytochrome P450 in the endoplasmic reticulum membrane. J Cell Biol. 1988 Aug;107(2):457–470. doi: 10.1083/jcb.107.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Mueckler M., Caruso C., Baldwin S. A., Panico M., Blench I., Morris H. R., Allard W. J., Lienhard G. E., Lodish H. F. Sequence and structure of a human glucose transporter. Science. 1985 Sep 6;229(4717):941–945. doi: 10.1126/science.3839598. [DOI] [PubMed] [Google Scholar]
  45. Mueckler M., Lodish H. F. Post-translational insertion of a fragment of the glucose transporter into microsomes requires phosphoanhydride bond cleavage. Nature. 1986 Aug 7;322(6079):549–552. doi: 10.1038/322549a0. [DOI] [PubMed] [Google Scholar]
  46. Nakayama N., Miyajima A., Arai K. Nucleotide sequences of STE2 and STE3, cell type-specific sterile genes from Saccharomyces cerevisiae. EMBO J. 1985 Oct;4(10):2643–2648. doi: 10.1002/j.1460-2075.1985.tb03982.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Nathans J., Thomas D., Hogness D. S. Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. Science. 1986 Apr 11;232(4747):193–202. doi: 10.1126/science.2937147. [DOI] [PubMed] [Google Scholar]
  48. Nelson D. R., Strobel H. W. On the membrane topology of vertebrate cytochrome P-450 proteins. J Biol Chem. 1988 May 5;263(13):6038–6050. [PubMed] [Google Scholar]
  49. Noda M., Ikeda T., Kayano T., Suzuki H., Takeshima H., Kurasaki M., Takahashi H., Numa S. Existence of distinct sodium channel messenger RNAs in rat brain. Nature. 1986 Mar 13;320(6058):188–192. doi: 10.1038/320188a0. [DOI] [PubMed] [Google Scholar]
  50. O'Tousa J. E., Baehr W., Martin R. L., Hirsh J., Pak W. L., Applebury M. L. The Drosophila ninaE gene encodes an opsin. Cell. 1985 Apr;40(4):839–850. doi: 10.1016/0092-8674(85)90343-5. [DOI] [PubMed] [Google Scholar]
  51. Olsen J., Cowell G. M., Kønigshøfer E., Danielsen E. M., Møller J., Laustsen L., Hansen O. C., Welinder K. G., Engberg J., Hunziker W. Complete amino acid sequence of human intestinal aminopeptidase N as deduced from cloned cDNA. FEBS Lett. 1988 Oct 10;238(2):307–314. doi: 10.1016/0014-5793(88)80502-7. [DOI] [PubMed] [Google Scholar]
  52. Ovchinnikov YuA, Arzamazova N. M., Arystarkhova E. A., Gevondyan N. M., Aldanova N. A., Modyanov N. N. Detailed structural analysis of exposed domains of membrane-bound Na+,K+-ATPase. A model of transmembrane arrangement. FEBS Lett. 1987 Jun 15;217(2):269–274. doi: 10.1016/0014-5793(87)80676-2. [DOI] [PubMed] [Google Scholar]
  53. Ovchinnikov YuA Rhodopsin and bacteriorhodopsin: structure-function relationships. FEBS Lett. 1982 Nov 8;148(2):179–191. doi: 10.1016/0014-5793(82)80805-3. [DOI] [PubMed] [Google Scholar]
  54. Porter T. D., Kasper C. B. Coding nucleotide sequence of rat NADPH-cytochrome P-450 oxidoreductase cDNA and identification of flavin-binding domains. Proc Natl Acad Sci U S A. 1985 Feb;82(4):973–977. doi: 10.1073/pnas.82.4.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Randall L. L., Hardy S. J. Correlation of competence for export with lack of tertiary structure of the mature species: a study in vivo of maltose-binding protein in E. coli. Cell. 1986 Sep 12;46(6):921–928. doi: 10.1016/0092-8674(86)90074-7. [DOI] [PubMed] [Google Scholar]
  56. Rapoport T. A. Extensions of the signal hypothesis--sequential insertion model versus amphipathic tunnel hypothesis. FEBS Lett. 1985 Jul 22;187(1):1–10. doi: 10.1016/0014-5793(85)81202-3. [DOI] [PubMed] [Google Scholar]
  57. Rapoport T. A. Protein translocation across and integration into membranes. CRC Crit Rev Biochem. 1986;20(1):73–137. doi: 10.3109/10409238609115901. [DOI] [PubMed] [Google Scholar]
  58. Sakaguchi M., Mihara K., Sato R. A short amino-terminal segment of microsomal cytochrome P-450 functions both as an insertion signal and as a stop-transfer sequence. EMBO J. 1987 Aug;6(8):2425–2431. doi: 10.1002/j.1460-2075.1987.tb02521.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Schneider C., Owen M. J., Banville D., Williams J. G. Primary structure of human transferrin receptor deduced from the mRNA sequence. Nature. 1984 Oct 18;311(5987):675–678. doi: 10.1038/311675b0. [DOI] [PubMed] [Google Scholar]
  60. Schofield P. R., Rhee L. M., Peralta E. G. Primary structure of the human beta-adrenergic receptor gene. Nucleic Acids Res. 1987 Apr 24;15(8):3636–3636. doi: 10.1093/nar/15.8.3636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Shaper N. L., Hollis G. F., Douglas J. G., Kirsch I. R., Shaper J. H. Characterization of the full length cDNA for murine beta-1,4-galactosyltransferase. Novel features at the 5'-end predict two translational start sites at two in-frame AUGs. J Biol Chem. 1988 Jul 25;263(21):10420–10428. [PubMed] [Google Scholar]
  62. Shaw A. S., Rottier P. J., Rose J. K. Evidence for the loop model of signal-sequence insertion into the endoplasmic reticulum. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7592–7596. doi: 10.1073/pnas.85.20.7592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Shaw A. S., Rottier P. J., Rose J. K. Evidence for the loop model of signal-sequence insertion into the endoplasmic reticulum. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7592–7596. doi: 10.1073/pnas.85.20.7592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Spiess M., Lodish H. F. An internal signal sequence: the asialoglycoprotein receptor membrane anchor. Cell. 1986 Jan 17;44(1):177–185. doi: 10.1016/0092-8674(86)90496-4. [DOI] [PubMed] [Google Scholar]
  65. Spiess M., Lodish H. F. Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6465–6469. doi: 10.1073/pnas.82.19.6465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Spiess M., Schwartz A. L., Lodish H. F. Sequence of human asialoglycoprotein receptor cDNA. An internal signal sequence for membrane insertion. J Biol Chem. 1985 Feb 25;260(4):1979–1982. [PubMed] [Google Scholar]
  67. Strubin M., Mach B., Long E. O. The complete sequence of the mRNA for the HLA-DR-associated invariant chain reveals a polypeptide with an unusual transmembrane polarity. EMBO J. 1984 Apr;3(4):869–872. doi: 10.1002/j.1460-2075.1984.tb01898.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Szczesna-Skorupa E., Browne N., Mead D., Kemper B. Positive charges at the NH2 terminus convert the membrane-anchor signal peptide of cytochrome P-450 to a secretory signal peptide. Proc Natl Acad Sci U S A. 1988 Feb;85(3):738–742. doi: 10.1073/pnas.85.3.738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Szczesna-Skorupa E., Kemper B. NH2-terminal substitutions of basic amino acids induce translocation across the microsomal membrane and glycosylation of rabbit cytochrome P450IIC2. J Cell Biol. 1989 Apr;108(4):1237–1243. doi: 10.1083/jcb.108.4.1237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Thorens B., Sarkar H. K., Kaback H. R., Lodish H. F. Cloning and functional expression in bacteria of a novel glucose transporter present in liver, intestine, kidney, and beta-pancreatic islet cells. Cell. 1988 Oct 21;55(2):281–290. doi: 10.1016/0092-8674(88)90051-7. [DOI] [PubMed] [Google Scholar]
  71. Walter P., Blobel G. Translocation of proteins across the endoplasmic reticulum III. Signal recognition protein (SRP) causes signal sequence-dependent and site-specific arrest of chain elongation that is released by microsomal membranes. J Cell Biol. 1981 Nov;91(2 Pt 1):557–561. doi: 10.1083/jcb.91.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Watanabe M., Hunt J. F., Blobel G. In vitro synthesized bacterial outer membrane protein is integrated into bacterial inner membranes but translocated across microsomal membranes. Nature. 1986 Sep 4;323(6083):71–73. doi: 10.1038/323071a0. [DOI] [PubMed] [Google Scholar]
  73. Waters M. G., Blobel G. Secretory protein translocation in a yeast cell-free system can occur posttranslationally and requires ATP hydrolysis. J Cell Biol. 1986 May;102(5):1543–1550. doi: 10.1083/jcb.102.5.1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Weinstein J. N., Blumenthal R., van Renswoude J., Kempf C., Klausner R. D. Charge clusters and the orientation of membrane proteins. J Membr Biol. 1982;66(3):203–212. doi: 10.1007/BF01868495. [DOI] [PubMed] [Google Scholar]
  75. Weinstein J., Lee E. U., McEntee K., Lai P. H., Paulson J. C. Primary structure of beta-galactoside alpha 2,6-sialyltransferase. Conversion of membrane-bound enzyme to soluble forms by cleavage of the NH2-terminal signal anchor. J Biol Chem. 1987 Dec 25;262(36):17735–17743. [PubMed] [Google Scholar]
  76. Wertz G. W., Collins P. L., Huang Y., Gruber C., Levine S., Ball L. A. Nucleotide sequence of the G protein gene of human respiratory syncytial virus reveals an unusual type of viral membrane protein. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4075–4079. doi: 10.1073/pnas.82.12.4075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Wessels H. P., Spiess M. Insertion of a multispanning membrane protein occurs sequentially and requires only one signal sequence. Cell. 1988 Oct 7;55(1):61–70. doi: 10.1016/0092-8674(88)90009-8. [DOI] [PubMed] [Google Scholar]
  78. Wickner W. T., Lodish H. F. Multiple mechanisms of protein insertion into and across membranes. Science. 1985 Oct 25;230(4724):400–407. doi: 10.1126/science.4048938. [DOI] [PubMed] [Google Scholar]
  79. Williams M. A., Lamb R. A. Determination of the orientation of an integral membrane protein and sites of glycosylation by oligonucleotide-directed mutagenesis: influenza B virus NB glycoprotein lacks a cleavable signal sequence and has an extracellular NH2-terminal region. Mol Cell Biol. 1986 Dec;6(12):4317–4328. doi: 10.1128/mcb.6.12.4317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Zerial M., Huylebroeck D., Garoff H. Foreign transmembrane peptides replacing the internal signal sequence of transferrin receptor allow its translocation and membrane binding. Cell. 1987 Jan 16;48(1):147–155. doi: 10.1016/0092-8674(87)90365-5. [DOI] [PubMed] [Google Scholar]
  81. Zerial M., Melancon P., Schneider C., Garoff H. The transmembrane segment of the human transferrin receptor functions as a signal peptide. EMBO J. 1986 Jul;5(7):1543–1550. doi: 10.1002/j.1460-2075.1986.tb04395.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. van Driel I. R., Goding J. W. Plasma cell membrane glycoprotein PC-1. Primary structure deduced from cDNA clones. J Biol Chem. 1987 Apr 5;262(10):4882–4887. [PubMed] [Google Scholar]
  83. von Heijne G. Analysis of the distribution of charged residues in the N-terminal region of signal sequences: implications for protein export in prokaryotic and eukaryotic cells. EMBO J. 1984 Oct;3(10):2315–2318. doi: 10.1002/j.1460-2075.1984.tb02132.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. von Heijne G., Gavel Y. Topogenic signals in integral membrane proteins. Eur J Biochem. 1988 Jul 1;174(4):671–678. doi: 10.1111/j.1432-1033.1988.tb14150.x. [DOI] [PubMed] [Google Scholar]

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