What type of signal sequence targets proteins to the endoplasmic reticulum (ER)?

The targeting of proteins to the endoplasmic reticulum (ER) is primarily facilitated by an N-terminal hydrophobic signal sequence. This signal sequence typically consists of a stretch of hydrophobic amino acids, which helps to initiate the translocation of the nascent polypeptide into the ER during synthesis.

When the protein is being synthesized by ribosomes, the presence of this hydrophobic signal sequence is detected by the signal recognition particle (SRP). The SRP binds to the signal sequence and pauses further translation until the ribosome is directed to the ER membrane. Once attached to the ER, the ribosome resumes translation, and the growing polypeptide chain is threaded through the translocon—a channel in the ER membrane—facilitating entry into the lumen of the ER or integration into the membrane itself.

In context, while other signal sequences may guide proteins to different cellular destinations, they do not specifically direct proteins to the ER as effectively as the N-terminal hydrophobic signal sequence. The hydrophilic or signal sequences at different positions do not possess the same function in ER targeting, making the N-terminal hydrophobic signal sequence the correct choice for this question.