title: Identification of Lassa virus glycoprotein signal peptide as a trans-acting maturation factor.
abstract: Lassa virus glycoprotein is translated as a precursor (pre-GP-C) into the lumen of the endoplasmic reticulum and is cotranslationally cleaved into the signal peptide and GP-C, before GP-C is proteolytically processed into its subunits GP1 and GP2. The signal peptide of pre-GP-C comprises 58 amino acids. The substitution of Lassa virus pre-GP-C signal peptide with another signal peptide still mediates translocation and the release of signal peptide but abolishes the proteolytic cleavage of GP-C into GP1 and GP2. Remarkably, cleavage of GP-C from these hybrid pre-GP-C substrates was restored on coexpression of the wild-type pre-GP-C signal peptide, indicating that the signal peptide functions as a trans-acting factor to promote Lassa virus GP-C processing. To our knowledge, this is the first report on a signal peptide that is essential for proteolytic processing of a secretory pathway protein.
authors.affiliation: Institut für Virologie der Philipps-Universität Marburg, Robert-Koch-Strasse 17, D-35037 Marburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Eichler
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.forename: Thomas
authors.initials: T
authors.lastname: Strecker
authors.forename: Markus
authors.initials: M
authors.lastname: Eickmann
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Klenk
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Garten
mesh_terms: D007836:Lassa virus / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D021382:Protein Sorting Signals / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism
chemical_list: D011498:Protein Precursors; D021382:Protein Sorting Signals; D015534:Trans-Activators; D014759:Viral Envelope Proteins; C066508:glycoprotein gp1, lassa virus; C077198:glycoprotein gp2, lassa virus