COMPLETE PRIMARY STRUCTURES AND PRESUMED FUNCTIONS OF IMMUNOGLOBULIN PRECURSORS

Abstract

The mRNA molecules coding for mouse immunoglobulin(Ig) light(L) chains program the cell free synthesis of precursors in which extra peptide segments precede the N-termini of the mature proteins, i.e., the extra piece is linked to the variable(V)-region (the N-terminal half of the L-chain). The complete primary structures of the N-terminal extra pieces of three K-type and three λ-type L-chain precursors were determined. Despite the fact that the extra pieces differ extensively in sequence (up to 73%) they share the following features: a high percentage of hydrophobic residues (69–75%), Met is the N-terminal residue, they are of comparable size (19–22 residues long) and contain fairly long peptide segments (16–19 residues) devoid of any charged residues. These structural features and other experiments indicate that: 1) the V-gene may be larger than hitherto realized; 2) the precursor seems to be the immediate translation product in the cell since the N-terminal Met was identified as the initiator residue; 3) in the cell the precursor is short lived, and the maturation process (cleavage of the extra piece) may regulate secretion of the mature protein; 4) the physiological role of the hydrophobic extra piece may be to favour interaction of the precursor with cell-membranes, in a manner similar to the function of the “hydrophobic domain” of membrane bound proteins. We propose two targets for interaction: a. The endoplasmic membranes, where the extra piece is cleaved from the precursor to yield mature protein destined for secretion; b. The cell-surface membrane, where the extra piece helps anchoring of the precursor to serve as the antigen-recognizing receptor. Preliminary studies on one Ig heavy(H)-chain precursor demonstrate that it contains a hydrophobic N-terminal extra piece (at least 18 residues long). The primary structure of the extra pieces of the precursors of the H-chain and L-chain, both of which are synthesized by the same myeloma cell, are different. Recently the precursor of the constant (C)-region polypeptide fragment (the carboxy terminal half of the L-chain) was found to contain an N-terminal extra piece (17 residues long) with primary structure identical to that of one of the extra pieces linked to the V-region in whole L-chain precursors. These findings suggest: 1. translocation of the extra piece from the V-region to the C-region; 2. independent expression of the C-gene associated with translocation of the DNA-segment coding for the extra piece.