Amino-Terminal Processing of Proteins: Hemoglobin South Florida, a Variant with Retention of Initiator Methionine and Nα-acetylation

The hemoglobin variant South Florida has been shown by protein sequencing and fast-atom-bombardment mass spectroscopy to have a substitution of methionine for the NH2-terminal valine of the β -globin chain. In addition, there was complete retention of the initiator methionine on the mutant polypeptide. Approximately 20% of the protein was acetylated at the NH2terminus of the β chain. A search of a comprehensive data bank of protein and gene sequences revealed 84 unrelated vertebrate proteins that have not undergone cleavage of leader sequences. A highly nonrandom distribution of residues at the NH2termini of these proteins predicts removal of the initiator methionine as well as NH2-terminal acetylation. Proteins that undergo removal commonly have serine, alanine, glycine, or valine, as the NH2-terminal residues. The first three residues favor Nα-acetylation. Proteins that retain the initiator methionine commonly have a charged residue or methionine at the second position. Information on Hb South Florida and other hemoglobins coupled with this survey of primary sequence provides insights into the NH2-terminal processing of proteins.