Maturation cleavage within the ectodomain of Lassa virus glycoprotein relies on stabilization by the cytoplasmic tail.
The Lassa virus glycoprotein consists of an ectodomain, a transmembrane anchor, and a cytoplasmic domain. It is synthesized as an inactive precursor and cleaved within the ectodomain to yield the mature form. Here, we show that this maturation cleavage can be abolished by mutation of single conserved amino acids within the cytoplasmic domain at the carboxy-terminus of the glycoprotein. Moreover, substitutions and deletions of multiple amino acids result in destabilization of the glycoprotein oligomers. These results indicate that conformation changes in the cytoplasmic domain travel across the membrane and subsequently abolish the maturation cleavage. Therefore, we postulate that the cytoplasmic domain is an important maturation factor stabilizing the overall conformation of the glycoprotein.
Schlie
Katrin
K
Institute of Virology, Philipps University of Marburg, Marburg, Germany.
Strecker
Thomas
T
Garten
Wolfgang
W
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007836:Lassa virus; D008969:Molecular Sequence Data; D009154:Mutation; D010447:Peptide Hydrolases / Q000378:metabolism; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D006023:Glycoproteins; D014764:Viral Proteins; D010447:Peptide Hydrolases