Mapping the landscape of the lymphocytic choriomeningitis virus stable signal peptide reveals novel functional domains.
The stable signal peptide (SSP) of the lymphocytic choriomeningitis virus surface glycoprotein precursor has several unique characteristics. The SSP is unusually long, at 58 amino acids, and contains two hydrophobic domains, and its sequence is highly conserved among both Old and New World arenaviruses. To better understand the functions of the SSP, a panel of point and deletion mutants was created by in vitro mutagenesis to target the highly conserved elements within the SSP. We were also able to confirm critical residues required for separate SSP functions by trans-complementation. Using these approaches, it was possible to resolve functional domains of the SSP. In characterizing our SSP mutants, we discovered that the SSP is involved in several distinct functions within the viral life cycle, beyond translocation of the viral surface glycoprotein precursor into the endoplasmic reticulum lumen. The SSP is required for efficient glycoprotein expression, posttranslational maturation cleavage of GP1 and GP2 by SKI-1/S1P protease, glycoprotein transport to the cell surface plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion.
Saunders
April A
AA
The Scripps Research Institute, Molecular and Integrative Neurosciences Department, Mailstop SP30-2020, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Ting
Joey P C
JP
Meisner
Jeffrey
J
Neuman
Benjamin W
BW
Perez
Mar
M
de la Torre
Juan Carlos
JC
Buchmeier
Michael J
MJ
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D008217:Lymphocytic choriomeningitis virus / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D025941:Protein Interaction Mapping; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D021382:Protein Sorting Signals / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D017384:Sequence Deletion; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
D008562:Membrane Glycoproteins; D011498:Protein Precursors; D021382:Protein Sorting Signals; D014764:Viral Proteins