Identification of an alternative signal peptide cleavage site of mouse monoclonal antibodies by mass spectrometry.

Signal peptide is normally cleaved at a very specific site by signal peptidase after co-translational translocation of cytoplasmic proteins across membrane. The molecular weights of the light chains and the heavy chains from five mouse monoclonal antibodies were analyzed. Three light chains from three antibodies had the predicted molecular weights. However, two light chains from the other two antibodies had a molecular weight of 87 Da higher. The two light chains had the same signal peptide sequences. Analysis by mass spectrometry and comparison of the amino acid sequences of the signal peptides indicated that the 87 Da increase was due to the addition of a serine residue to the N-termini of the two light chains from an alternative signal peptide cleavage.