1. Top of page
  2. Abstract

The translocation site (translocon), at which nascent polypeptides pass through the endoplasmic reticulum membrane, contains a component previously called ‘signal sequence receptor’ that is now renamed as ‘translocon-associated protein’ (TRAP). Two glycosylated subunits of the TRAP complex have been identified before (α and β subunits). We now show that the TRAP complex is actually comprised of four membrane proteins (α, β, γ, δ), present in a stoichiometric relation, which are genuine neighbours in intact microsomes. The amino acid sequences of the additional, non-glycosylated subunits were deduced from cloning of the corresponding cDNAs. The δ subunit spans the membrane only once and has its major portion, containing a disulfide bridge, at the lumenal side. The γ subunit is predicted to span the membrane four times.


endoplasmic reticulum

TRAM protein

translocating-chain-associating membrane protein


translocon-associated protein


  1. Top of page
  2. Abstract
  • 1
    Walter, P. & Lingappa, V. R. (1986) Mechanism of protein translocation across the endoplasmic reticulum membrane, Annu. Rev. Cell Biol. 2, 499516.
  • 2
    Rapoport, T. A. (1992) Transport of proteins across the endoplasmic reticulum membrane, Science 258, 931936.
  • 3
    Wiedmann, M., Kurzchalia, T. V., Hartmann, E. & Rapoport, T. A. (1987) A signal sequence receptor in the endoplasmic reticulum membrane, Nature 328, 830833.
  • 4
    Krieg, U. C., Johnson, A. E. & Walter, P. (1989) Protein translocation across the endoplasmic reticulum membrane: Identification by photocrosslinking of a 39-kDa integral membrane glycoprotein as part of a putative translocation tunnel, J. Cell Biol. 109, 20332043.
  • 5
    Wiedmann, M., Görlich, P., Hartmann, E., Kurzchalia, T. V. & Rapoport, T. A. (1989) Photocrosslinking demonstrates proximity of the 34-kDa membrane protein to different portions of preprolactin during translocation through the endoplasmic reticulum, FEBS Lett. 257, 263268.
  • 6
    Görlich, D., Prehn, S., Hartmann, E., Herz, J., Otto, A., Kraft, R., Wiedmann, M., Knespel, S., Dobberstein, B. & Rapoport, T. A. (1990) The signal sequence receptor has a second subunit and is part of a translocation complex in the endoplasmic reticulum as probed by bifunctional reagents, J. Cell Biol. 111, 22832294.
  • 7
    High, S., Görlich, D., Wiedmann, M., Rapoport, T. A. & Dobberstein, B. (1991) The identification of proteins in the proximity of signal-anchor sequences during their targeting to and insertion into the membrane of the ER, J. Cell Biol. 113, 3544.
  • 8
    Görlich, D., Hartmann, E., Prehn, S. & Rapoport, T. A. (1992) A protein of the endoplasmic reticulum involved early in polypeptide translocation, Nature 357, 4752.
  • 9
    Görlich, D., Prehn, S., Hartmann, E., Kalies, K.-U. & Rapoport, T. A. (1992) A mammalian homolog of Sec61p and SecYp is associated with ribosomes and nascent polypeptides during translocation, Cell 71, 489503.
  • 10
    Hartmann, E., Wiedmann, M. & Rapoport, T. A. (1989) A membrane component of the endoplasmic reticulum that may be essential for protein translocation, EMBO J. 8, 22252229.
  • 11
    Migliaccio, G., Nicchitta, C. V. & Blobel, G. (1992) The signal sequence receptor, unlike the signal recognition particle receptor, is not essential for protein translocation, J. Cell Biol. 117, 1525.
  • 12
    Vogel, F., Hartmann, E., Görlich, D. & Rapoport, T. A. (1990) Segregation of the signal sequence receptor protein in the rough endoplasmic reticulum membrane, Eur. J. Cell Biol. 53, 197202.
  • 13
    Collins, P. G. & Gilmore, R. (1991) Ribosome binding to the endoplasmic reticulum: a 180-kDa protein identified by crosslinking to membrane-bound ribosomes is not required for ribosome binding activity, J. Cell Biol. 114, 639649.
  • 14
    Prehn, S., Herz, J., Hartmann, E., Kurzchalia, T. V., Frank, R., Römisch, K., Dobberstein, B. & Rapoport, T. A. (1990) Structure and biosynthesis of the signal sequence receptor, Eur. J. Biochem. 188, 439445.
  • 15
    Harlow, E. & Lane, D. (1988) Antibodies: a laboratory manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor NY .
  • 16
    Walter, P. & Blobel, G. (1983) Preparation of microsomal membranes for cotranslational protein translocation, Methods Enzymol. 96, 557561.
  • 17
    Walter, P., Ibrahimi, I. & Blobel, G. (1981) Translocation of proteins across the endoplasmic reticulum. I. Signal recognition protein (SRP) binds to in-vitro-assembled polysomes synthesizing secretory protein, J. Cell Biol. 91, 545550.
  • 18
    Laemmli, U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature 227, 680685.
  • 19
    von Heijne, G. (1986) A new method for predicting signal peptide cleavage sites, Nucleic Acids Res. 14, 46834690.
  • 20
    Kozak, M. (1989) The scanning model for translation: an update, J. Cell Biol. 108, 229241.
  • 21
    McCombie, W. R., Adams, M. D., Kelley, J. M., Fitzgerald, M. G., Utterback, T. R., Khan, M., Dubnick, M., Kerlavage, A. R., Venter, J. & Fields, C. (1992) Caenorhabditis elegans expressed sequence tags reveal gene families and potential disease gene homologues, Nature Genet. 1, 124131.
  • 22
    Wada, I., Rindress, D., Cameron, P. H., Ou, W.-J., Doherty II, J. J., Louvard, D., Bell, A. W., Dignard, D., Thomas, D. Y. & Bergeron, J. J. M. (1991) SSRα and associated calnexin are major calcium binding proteins of the endoplasmic reticulum membrane, J. Biol. Chem. 266, 1959919610.
  • 23
    Kelleher, D. J., Kreibich, G. & Gilmore, R. (1992) Oligosaccharyltransferase activity is associated with a protein complex composed of ribophorins I and II and a 48-kDa protein, Cell 69, 5565.
  • 24
    Yu, Y., Sabatini, D. D. & Kreibich, G. (1990) Antiribophorin antibodies inhibit targeting to the ER membrane of ribosomes containing nascent secretory polypeptides, J. Cell Biol. 111, 13351342.
  • 25
    Crimaudo, C., Hortsch, M., Gausepohl, H. & Meyer, D. I. (1987) Human ribophorins I and II: primary structure and membrane topology of two highly conserved rough endoplasmic reticulum-specific glycoproteins, EMBO J. 6, 7582.