Identification of Lassa virus glycoprotein signal peptide as a trans-acting maturation factor.
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.
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
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
D011498:Protein Precursors; D021382:Protein Sorting Signals; D015534:Trans-Activators; D014759:Viral Envelope Proteins; C066508:glycoprotein gp1, lassa virus; C077198:glycoprotein gp2, lassa virus