What is a signal peptide and how does it direct protein localization?

• A. A short N-terminal sequence that directs the ribosome to the endoplasmic reticulum for secretion or membrane insertion; often cleaved after targeting.
• B. A C-terminal sequence that anchors proteins to the mitochondrion.
• C. An internal hydrophobic region that exports to the Golgi.
• D. A sequence at the 3' end that targets to lysosome.

Answer: (B)

Signal peptides are short sequences at the very start of a protein (an N-terminal signal) that guide the ribosome to the endoplasmic reticulum and kick off the secretory pathway. As the protein is synthesized, the signal peptide is recognized by the signal recognition particle, which pauses translation and helps dock the ribosome to the ER translocon. The growing protein is then threaded into the ER lumen or embedded in the ER membrane. Most signal peptides are cleaved off inside the ER, and the protein proceeds toward secretion or membrane localization. This explains why many secreted and membrane proteins have an N-terminal signal that is removed after targeting.

Other descriptions don’t fit this mechanism: a C-terminal sequence that anchors proteins to mitochondria involves a mitochondrial targeting signal, not an ER-directed signal peptide; an internal hydrophobic region can act as a signal anchor but is not the cleavable N-terminal signal that directs the entire protein into the ER; and a sequence at the 3' end that targets to lysosomes doesn’t describe how the secretory pathway is initiated.