Another factor besides hydrophobicity can affect signal peptide interaction with signal recognition particle

Translocation of alkaline extracellular protease (AEP) into the endoplasmic reticulum of Yarrowia lipolytica is cotranslational and signal recognition particle (SRP)dependent, whereas translocation of Firm AFP (proline to methionine at position 17, second amino acid in the pro-region) is posttranslational and SRP-independent. Firm signal peptide mutations that resulted in more rapid SRP-dependent translocation of AEP precursor were isolated. Most of these mutations significantly increased hydrophobicity, but the A12P/P17M mutation did not. The switch from SRP-dependent to SRP-independent translocation without a decrease in hydrophobicity (wild type to P17M) and restoration of SRP-dependent translocation without an increase in hydrophobicity (P17M to A12P/P17M) indicate that some factor(s) in addition to hydrophobicity determines selection of targeting pathway. Models of extended forms of wild type and A12P/P17M signal peptides are kinked, whereas the P17M signal peptide is relatively straight. Possibly the conformation/orientation of signal peptides at the ribosomal surface affects SRP binding and consequently the targeting route to the endoplasmic reticulum. Kinked signal peptides might approach SRP more closely more often. Most likely, these effects were only detectable because of the short length and low average hydrophobicity of the AEP signal peptide.