Summary
Investigation of possible variations between prokaryotic and eukaryotic signal sequences of exported proteins has revealed unexpected differences. Apart from the known similarities (presence of a core hydrophobic sequence preceded by a positively charged amino terminus and followed by a flexible structure), we have found that the core is much more rigid in eukaryotic signals than in their prokaryotic counterparts, and that at both ends the constraints are much more stringent in bacteria than in human cells. The differences have been summarized as a set of 17 criteria describing noteworthy features discriminating between the two classes of signal peptides. The program we used permitted each class of sequences to be learned;Escherichia coli sequences were well learned (i.e., they could be recognized by the programs as having common features), whereas human sequences were found to exhibit a much wider variation. Thus it was possible to propose a consensus in the case of the bacterial peptides, but none (or a much looser one) in the case of the human sequences. Two sequences were exceptional among theE. coli signal peptides, those of lipoprotein and plasmid-borne beta-lactamase, suggesting that they have special origins or destinations. Finally, the differences found strongly suggest that the mode of secretion is rather different in the two types of organisms, in spite of the common features of the signal sequences.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Austen BM (1979) Predicted secondary structures of amino-terminal extension sequences of secreted proteins. FEBS Lett 103:308–313
Bedouelle H, Hofnung M (1981) On the role of the signal peptide in the initiation of protein exportation. In: Pulman B (ed) Intermolecular forces. Reidel, Dordrecht Boston, pp 361–372
Blobel G, Dobberstein B (1975a) 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 67: 835–851
Blobel G, Dobberstein B (1975b) Transfer of proteins across membranes. II. Reconstitution of functional rough microsomes from heterologous components. J Cell Biol 67:852–862
Buchanan BG, Feigenbaum EA (1978) Dendral and meta-dendral: their applications dimensions.Artificial Intelligence 11: 5–24
Burley SA, Petsko GA (1985) Aromatic-aromatic interaction: a mechanism of protein structure stabilization. Science 229: 23–28
Burns DM, Beacham IR (1985) Rare codons inE. coli andS. typhimurium signal sequences. FEBS Lett 189:318–322
Cohen PR, Feigenbaum EA (1982) The handbook of artificial intelligence, vol 3. Pitman, London, chapter 14
Dev IK, Ray PH (1984) Rapid assay and purification of a unique signal peptidase that processes the prolipoprotein fromEscherichia coli. J Biol Chem 259:11114–11120
Engelman DM, Steitz TA (1981) The spontaneous insertion of proteins into and across membranes: the helical hairpin hypothesis. Cell 23:411–422
Gascuel O (1986) PLAGE: A way to give and use knowledge in a learning program. In: Proceedings of the European Working Session on Learning, L.R.I., Orsay (available upon request)
Groarke JM, Mahoney WC, Hope JN, Furlong CE, Robb FT, Zalkin H, Hermondson MA (1983) The amino acid sequence ofd-ribose-binding protein fromEscherichia coli K-12. J Biol Chem 258:12952–12956
Harrison TM, Brownlee GC, Milstein C (1974) Studies on polysome-membrane interactions in mouse myeloma cells. Eur J Biochem 47:613–620
Inouye I, Franceschini T, Sato M, Itakura K, Inouye M (1983) Prolipoprotein signal peptidase ofEscherichia coli requires a cysteine residue at the cleavage site. EMBO J 2:87–91
Jackson ME, Pratt JM, Stoker NG, Holland IB (1985) An inner membrane protein N-terminal signal is able to promote efficient localisation of an outer membrane protein inEscherichia coli. EMBO J 4:2377–2383
Kaczorek M, Delpeyroux F, Chenciner N, Streeck RE, Murphy JR, Boquet P, Tiollais P (1983) Nucleotide sequence and expression in the diphtheria tox228 gene inEscherichia coli. Science 221:855–858
Kelly RB (1985) Pathways of protein secretion in eukaryotes. Science 230:25–32
Lenat DB (1977) The ubiquity of discovery.Artificial Intelligence 9:257–285
Meyer DI, Krause E, Dobberstein B (1982) Secretory protein translocation across membranes—the role of the “docking protein.” Nature 297:647–650
Mézes PF, Lampen O (1985) Secretion of protein by bacilli. In: Dubnau DA (ed) The molecular biology of the bacilli, vol II. Academic Press, New York, pp 159–180
Milstein C, Brownlee GG, Harrison TM, Mathews MB (1972) A possible precursor of immunoglobulin light chains. Nature (New Biol) 239:117–120
Mitchell TM, Utgoff PE, Banerji RB (1983) Learning by experimentation: acquiring and refining problem-solving heuristics. In: Michalski RS, Carbonell JG, Mitchell TM (eds) Machine learning. Tioga, Palo Alto, California, pp 163–190
Oxender DL, Landick R, Nazos P, Copeland BR (1984) Role of membrane potential in protein folding and secretion inEscherichia coli. Microbiology 1984:4–7
Perlman D, Halvorson HA (1983) A putative signal peptidase recognition site and sequence in eukaryotic and prokaryotic signal peptides. J Mol Biol 167:391–409
Pugsley AP, Schwartz M (1985) Export and secretion of proteins by bacteria. FEMS Microbiol Rev 32:3–38
Schwartz RM, Dayhoff MO (1978) In: Dayhoff MO (ed) Atlas of protein sequence and structure, vol 5. National Biomedical Research Foundation, Washington, DC, pp 353–358
Simon H (1979) Models of Discovery. Reidel, Dordrecht Boston
Steinmetz M, Le Coq D, Aymerich S, Gonzy-Tréboul G, Gay P (1985) The DNA sequence of the gene for the secretedBacillus subtilis enzyme levansucrase and its genetic control sites. Mol Gen Genet 200:220–228
Vlasuk GP, Inouye S, Ito H, Itakura K, Inouye M (1983) Effects of the complete removal of basic amino acid residues from the signal peptide on secretion of lipoprotein inEscherichia coli. J Biol Chem 258:7141–7148
von Heijne G (1981) Membrane proteins: the amino acid composition of membrane-penetrating segments. Eur J Biochem 116:419–422
von Heijne G (1983) Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem 133:17–21
Walter P, Blobel G (1981) 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 91:557–562
Watson MEE (1984) Compilation of published signal sequences. Nucleic Acids Res 12:5145–5164
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gascuel, O., Danchin, A. Protein export in prokaryotes and eukaryotes: Indications of a difference in the mechanism of exportation. J Mol Evol 24, 130–142 (1986). https://doi.org/10.1007/BF02099961
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02099961