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. 1987 Apr;84(7):1960–1964. doi: 10.1073/pnas.84.7.1960

On the transfer of integral proteins into membranes.

S J Singer, P A Maher, M P Yaffe
PMCID: PMC304561  PMID: 3470770

Abstract

We have earlier proposed a molecular mechanism for the translocation of hydrophilic proteins across membranes that accounts for the experimental facts and meets the restrictions that we stipulate for such a mechanism. In particular, the restrictions are that translocation occurs by successive segments of the polypeptide chain and that the ionic groups of the polypeptide remain in contact with water throughout the translocation process. The evidence indicates that the transfer of integral proteins into membranes very likely uses the same molecular machinery as does the translocation of hydrophilic proteins across membranes. Here we show how the mechanism we have proposed for translocation can also be utilized in the intercalation of known types of integral proteins, accounting for their specific topologies in the membrane.

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Selected References

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

  1. Blobel G. Intracellular protein topogenesis. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1496–1500. doi: 10.1073/pnas.77.3.1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blok J., Air G. M., Laver W. G., Ward C. W., Lilley G. G., Woods E. F., Roxburgh C. M., Inglis A. S. Studies on the size, chemical composition, and partial sequence of the neuraminidase (NA) from type A influenza viruses show that the N-terminal region of the NA is not processed and serves to anchor the NA in the viral membrane. Virology. 1982 May;119(1):109–121. doi: 10.1016/0042-6822(82)90069-1. [DOI] [PubMed] [Google Scholar]
  3. Braell W. A., Lodish H. F. The erythrocyte anion transport protein is contranslationally inserted into microsomes. Cell. 1982 Jan;28(1):23–31. doi: 10.1016/0092-8674(82)90371-3. [DOI] [PubMed] [Google Scholar]
  4. Coleman J., Inukai M., Inouye M. Dual functions of the signal peptide in protein transfer across the membrane. Cell. 1985 Nov;43(1):351–360. doi: 10.1016/0092-8674(85)90040-6. [DOI] [PubMed] [Google Scholar]
  5. Dalbey R. E., Wickner W. Leader peptidase catalyzes the release of exported proteins from the outer surface of the Escherichia coli plasma membrane. J Biol Chem. 1985 Dec 15;260(29):15925–15931. [PubMed] [Google Scholar]
  6. Engelman D. M., Steitz T. A. The spontaneous insertion of proteins into and across membranes: the helical hairpin hypothesis. Cell. 1981 Feb;23(2):411–422. doi: 10.1016/0092-8674(81)90136-7. [DOI] [PubMed] [Google Scholar]
  7. Hase T., Müller U., Riezman H., Schatz G. A 70-kd protein of the yeast mitochondrial outer membrane is targeted and anchored via its extreme amino terminus. EMBO J. 1984 Dec 20;3(13):3157–3164. doi: 10.1002/j.1460-2075.1984.tb02274.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hol W. G. The role of the alpha-helix dipole in protein function and structure. Prog Biophys Mol Biol. 1985;45(3):149–195. doi: 10.1016/0079-6107(85)90001-x. [DOI] [PubMed] [Google Scholar]
  9. Khorana H. G., Gerber G. E., Herlihy W. C., Gray C. P., Anderegg R. J., Nihei K., Biemann K. Amino acid sequence of bacteriorhodopsin. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5046–5050. doi: 10.1073/pnas.76.10.5046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lenard J., Singer S. J. Protein conformation in cell membrane preparations as studied by optical rotatory dispersion and circular dichroism. Proc Natl Acad Sci U S A. 1966 Dec;56(6):1828–1835. doi: 10.1073/pnas.56.6.1828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Maher P. A., Singer S. J. Disulfide bonds and the translocation of proteins across membranes. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9001–9005. doi: 10.1073/pnas.83.23.9001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Mueckler M., Lodish H. F. The human glucose transporter can insert posttranslationally into microsomes. Cell. 1986 Feb 28;44(4):629–637. doi: 10.1016/0092-8674(86)90272-2. [DOI] [PubMed] [Google Scholar]
  14. Rose J. K., Gallione C. J. Nucleotide sequences of the mRNA's encoding the vesicular stomatitis virus G and M proteins determined from cDNA clones containing the complete coding regions. J Virol. 1981 Aug;39(2):519–528. doi: 10.1128/jvi.39.2.519-528.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rothman J. E., Lodish H. F. Synchronised transmembrane insertion and glycosylation of a nascent membrane protein. Nature. 1977 Oct 27;269(5631):775–780. doi: 10.1038/269775a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Singer S. J., Maher P. A., Yaffe M. P. On the translocation of proteins across membranes. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1015–1019. doi: 10.1073/pnas.84.4.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Singer S. J., Nicolson G. L. The fluid mosaic model of the structure of cell membranes. Science. 1972 Feb 18;175(4023):720–731. doi: 10.1126/science.175.4023.720. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Unwin P. N., Ennis P. D. Calcium-mediated changes in gap junction structure: evidence from the low angle X-ray pattern. J Cell Biol. 1983 Nov;97(5 Pt 1):1459–1466. doi: 10.1083/jcb.97.5.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wada A. The alpha-helix as an electric macro-dipole. Adv Biophys. 1976:1–63. [PubMed] [Google Scholar]
  22. Yost C. S., Hedgpeth J., Lingappa V. R. A stop transfer sequence confers predictable transmembrane orientation to a previously secreted protein in cell-free systems. Cell. 1983 Oct;34(3):759–766. doi: 10.1016/0092-8674(83)90532-9. [DOI] [PubMed] [Google Scholar]

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