Lassa virus glycoprotein signal peptide displays a novel topology with an extended endoplasmic reticulum luminal region.
Lassa virus glycoprotein C (GP-C) is translated as a precursor (preGP-C) into the lumen of the endoplasmic reticulum (ER) and cotranslationally cleaved into the signal peptide and immature GP-C before GP-C is proteolytically processed into its subunits, GP-1 and GP-2, which form the mature virion spikes. The signal peptide of preGP-C comprises 58 amino acids and contains two distinct hydrophobic domains. Here, we show that each hydrophobic domain alone can insert preGP-C into the ER membrane. Furthermore, we demonstrate that the native signal peptide only uses the N-terminal hydrophobic domain for membrane insertion, exhibiting a novel type of a topology for signal peptides with an extended ER luminal part, which is essential for proteolytic processing of GP-C into GP-1 and GP-2.
Eichler
Robert
R
Institut für Virologie der Philipps-Universität Marburg, Robert-Koch-Strasse 17, D-35037 Marburg, Germany.
Lenz
Oliver
O
Strecker
Thomas
T
Eickmann
Markus
M
Klenk
Hans-Dieter
HD
Garten
Wolfgang
W
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005822:Genetic Vectors; D006023:Glycoproteins / Q000737:chemistry*; D006026:Glycoside Hydrolases / Q000494:pharmacology; D007150:Immunohistochemistry; D007836:Lassa virus / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D014709:Vero Cells
D006023:Glycoproteins; D021382:Protein Sorting Signals; D006026:Glycoside Hydrolases