Publikationsdatenbank

Co-translational processing of glycoprotein 3 from equine arteritis virus: N-glycosylation adjacent to the signal peptide prevents cleavage (2013)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Matczuk, Anna Karolina (WE 5)

Kunec, Dusan (WE 5)

Veit, Michael (WE 5)

Quelle

The journal of biological chemistry

Bandzählung: 288

Heftzählung: 49

Seiten: 35396 – 35405

ISSN: 0021-9258

Sprache

Englisch

Verweise

DOI: 10.1074/jbc.M113.505420

Pubmed: 24142700

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
Gebäude 35
14163 Berlin
+49 30 838 51833
viro@zedat.fu-berlin.de

Abstract / Zusammenfassung

Signal peptide cleavage and N-glycosylation of proteins are co-translational processes, but little is known about their interplay if they compete for adjacent sites. Here we report two unique findings for processing of glycoprotein 3 of equine arteritis virus. Glycoprotein 3 (Gp3) contains an N-terminal signal peptide, which is not removed, although bioinformatics predicts cleavage with high probability. There is an overlapping sequon, NNTT, adjacent to the signal peptide that we show to be glycosylated at both asparagines. Exchanging the overlapping sequon and blocking glycosylation allows signal peptide cleavage, indicating that carbohydrate attachment inhibits processing of a potentially cleavable signal peptide. Bioinformatics analyses suggest that a similar processing scheme may exist for some cellular proteins. Membrane fractionation and secretion experiments revealed that the signal peptide of Gp3 does not act as a membrane anchor, indicating that it is completely translocated into the lumen of the endoplasmic reticulum. Membrane attachment is caused by the hydrophobic C terminus of Gp3, which, however, does not span the membrane but rather attaches the protein peripherally to endoplasmic reticulum membranes.