Synthetic signal peptide and analogs display different activities in mammalian and plant in vitro secretion systems.
The biological properties of four chemically synthesized signal peptides were compared in mammalian (rabbit reticulocyte) and plant (wheat germ) cell-free protein secretion systems. The precursor-specific region of bovine pre-proparathyroid hormone (preproPTH), [D-Tyr-(+1)]preproPTH-(-29-+1)amide, and a sulfur-free analog, [Nle-(-25), Nle-(-21), Nle-(-18), Ala-(-14), D-Tyr-(+1)]preproPTH-(-29-+1)amide, inhibit the processing of an unrelated precursor protein (pre-prolactin) to its mature secreted form (prolactin) in the mammalian system. In the plant system supplemented with signal recognition particle, the signal peptides arrest translation of both secretory (preprolactin) and cytoplasmic (globin) proteins. One analog, [Nle-(-25), Nle-(-21), Asp-(-18), Ala-(-14), D-Tyr-(+1)]preproPTH-(-29-+1)amide, inhibits preprotein processing in the mammalian system but fails to induce translation arrest in the plant system. A truncated peptide, [N alpha-AcLeu-(-17), Ala-(-14), D-Tyr-(+1)]preproPTH-(-17-+1)amide, lacking the N-terminal (positively charged) region and a portion of the hydrophobic core region, is inactive in both systems. These studies demonstrate that the chemically synthesized signal region of a precursor protein interacts directly with signal recognition particle and functionally mimics the proposed properties of a native signal sequence linked to a nascent protein as it emerges from the ribosome during biosynthesis, and an analog of the signal peptide reveals fundamental differences between the components involved in the protein secretion apparatus in mammals and plants.
D000595:Amino Acid Sequence; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D005914:Globins / Q000096:biosynthesis; D066298:In Vitro Techniques; D008322:Mammals; D010281:Parathyroid Hormone / Q000494:pharmacology; D010944:Plants; D011388:Prolactin / Q000096:biosynthesis; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis / Q000494:pharmacology; D021382:Protein Sorting Signals / Q000378:metabolism*; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism
D010281:Parathyroid Hormone; D011498:Protein Precursors; D021382:Protein Sorting Signals; C017671:preprolactin; C019056:preproparathormone; D011388:Prolactin; D005914:Globins