The Nβ motif of NaTrxh directs secretion as an endoplasmic reticulum transit peptide and variations might result in different cellular targeting

PLoS One. 2023 Oct 12;18(10):e0287087. doi: 10.1371/journal.pone.0287087. eCollection 2023.

Abstract

Soluble secretory proteins with a signal peptide reach the extracellular space through the endoplasmic reticulum-Golgi conventional pathway. During translation, the signal peptide is recognised by the signal recognition particle and results in a co-translational translocation to the endoplasmic reticulum to continue the secretory pathway. However, soluble secretory proteins lacking a signal peptide are also abundant, and several unconventional (endoplasmic reticulum/Golgi independent) pathways have been proposed and some demonstrated. This work describes new features of the secretion signal called Nβ, originally identified in NaTrxh, a plant extracellular thioredoxin, that does not possess an orthodox signal peptide. We provide evidence that other proteins, including thioredoxins type h, with similar sequences are also signal peptide-lacking secretory proteins. To be a secretion signal, positions 5, 8 and 9 must contain neutral residues in plant proteins-a negative residue in position 8 is suggested in animal proteins-to maintain the Nβ motif negatively charged and a hydrophilic profile. Moreover, our results suggest that the NaTrxh translocation to the endoplasmic reticulum occurs as a post-translational event. Finally, the Nβ motif sequence at the N- or C-terminus could be a feature that may help to predict protein localisation, mainly in plant and animal proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Endoplasmic Reticulum* / metabolism
  • Golgi Apparatus / metabolism
  • Plants
  • Protein Sorting Signals*
  • Protein Transport

Substances

  • Protein Sorting Signals

Grants and funding

This work was supported by Consejo Nacional de Ciencia y Tecnología – México (240927); Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México (PAPIIT-IN230920); and Facultad de Ciencias, UNAM. A postgraduate fellowship was provided to A.Z-G by Consejo Nacional de Ciencia y Tecnología. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.