Partial amino-acid sequence of the precursor of an immunoglobulin light chain containing NH2-terminal pyroglutamic acid.
Analyses of amino-acid sequences of the total cell-free products programmed by the mRNA of MOPC-104E gamma light (L)-chain show that over 95% of the products have sequences of a distinct protein that correspond to the L-chain precursor. In this precursor an extra piece is coupled to the NH2-terminus of the mature L-chain. Analyses of products labeled with [3H]alanine, [3H]leucine, and [3H]proline demonstrate that the extra piece is composed of at least 18 residues. Analyses of [35S]methione-labeled product indicate that the extra piece may contain an additional NH2-terminal methionine, which is detected in about 10% of the molecules. Partial recovery of the NJ2-terminal methionine (alanine, leucine, and proline are recovered in yields close to theoretical, greater than 95%) suggests that it is the initiator methionine, which is known to be short lived in eukaryotes due to rapid hydrolysis. Thus, the extra piece seems to be 19 residues in length, and it contains one methionine at the NH2-terminus, three alanines at positions 2, 12, and 17, and five leucines at positions 6, 8, 10, 11, and 13. The close gathering of leucine residues, as well as their abundance (26%), suggest that the extra piece would be quite hydrophobic. Hydrophobicity seems to be a general property of the extra piece, since similar clusters of leucine were found in the precursors of 3 KL-chains (Burstein, Y. & Schechter, I. (1976) Biochem. J. 157, 145-151). The NH2-terminus of the mature MOPC-104E gamma L-chain is blocked by pyroglutamic acid. The fact that in the precursor a peptide segment precedes this NH2-terminus establishes that pyroglutamic acid is not the initiator residue for synthesis of the L-chain. Apparently, the pyroglutamic acid is formed by cyclization of glutamic acid or glutamine during cleavage of the extra piece to yield the mature L-chain.
D000595:Amino Acid Sequence; D000818:Animals; D002474:Cell-Free System; D005260:Female; D005971:Glutamates / Q000032:analysis; D007147:Immunoglobulin Light Chains / Q000032:analysis* / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009194:Myeloma Proteins / Q000032:analysis* / Q000096:biosynthesis; D011498:Protein Precursors / Q000032:analysis* / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism
D005971:Glutamates; D007147:Immunoglobulin Light Chains; D009194:Myeloma Proteins; D011498:Protein Precursors; D012333:RNA, Messenger