Practice question

Specificity of protein localization originates from signal sequences, with N-terminal signals directing either secretory or mitochondrial pathways depending on physicochemical properties. Classical secretory signal peptide of about 20 residues with central hydrophobic stretch targets nascent chain cotranslationally to endoplasmic reticulum via signal recognition particle and Sec61 translocon, after which protein traffics via vesicular transport to Golgi apparatus for glycan modification and sorting to lysosome via mannose-6-phosphate tag generated in cis Golgi, to plasma membrane, or extracellular secretion. Mitochondrial presequence also N-terminal but instead forms positively charged amphipathic helix rich in arginine, lysine, lacking hydrophobic core, recognized post-translationally by TOM complex. Other organelles use distinct signals: nuclear localization uses short basic lysine clusters, peroxisomal PTS2 uses N-terminal RTx5 motif while PTS1 uses C-terminal SKL, chloroplast transit peptide similar to mitochondrial but more serine rich. Thus N-terminal signal broadly directs to endomembrane system ending at Golgi or mitochondria, depending on helix character, ensuring compartment identity.