Exploring the context of diacidic motif D-E as a signal for unconventional protein secretion in eukaryotic proteins

Abstract

ABSTRACTUnconventional protein secretion (UPS) is an important phenomenon with fundamental implications to cargo export. How eukaryotic proteins transported by UPS are recognized without a conventional signal peptide has been an open question. It was recently observed that a diacidic amino acid motif (ASP-GLU or DE) is necessary for the secretion of superoxide dismutase 1 (SOD1) from yeast under nutrient starvation. Taking cue from this discovery, we explore the hypothesis of whether the diacidic motif DE, which can occur fairly ubiquitously, along with its context, can be a generic signal for unconventional secretion of proteins. Two different definitions of context were evaluated: structural order and charge signature in the neighborhood of DE as one, and the nature of the amino acid insertion (‘X’) when a D-X-E motif is present, as another. We observe that among the eukaryotic proteins we studied, the odds of the protein being secreted are higher when the DE motif occurs in the disordered region of the protein, with higher hydrophobicity and lower charge or when the insertion X has a propensity for phosphorylation.