Marked hydrophobicity of the NH2-terminal extra piece of immunoglobulin light-chain precursors: possible physiological functions of the extra piece.
- 1 September 1976
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 73 (9), 3273-3277
- https://doi.org/10.1073/pnas.73.9.3273
Abstract
MRNA coding for mouse immunoglobulin L-chains direct the cell-free synthesis of precursors in which extra peptide segments precede the NH2-termini of the mature proteins. The abundance (18-30%) of leucine residues in the extra piece indicates that it is quite hydrophobic. The study described here was done to determine the positions of all hydrophobic residues by sequencing 2 .kappa.-type L-chain precursors that were labeled with: [3H]Ala, [3H]Val, [3H]Leu, [3H]Ile, [3H]Thr, [3H]Pro, [3H]Phe, [3H]Tyr, [3H]Trp, [35S]Met and [35S]Cys. The partial sequences (and sizes) of the extra pieces obtained are as follows: in MOPC-321 precursor, Met-X-Thr-X-Thr-Leu-Leu-Leu-Trp-Val-Leu-Leu-Leu-Trp-Val-Pro-X-X-Thr-X-(20 residues; X is unknown); in MOPC-41 precursor, Met-X-Met-X-Ala-Pro-Ala-X-Ile-Phe-X-Phe-Leu-Leu-Leu-Leu-Phe-Pro-X-Thr-X-Cys-(22 residues). Despite the fact that these extra pieces differ extensively in sequence (68%), both of them are highly enriched with hydrophobic residues (75% in MOPC-321, 73% in MOPC-41). This marked hydrophobicity suggests that the extra piece favors interaction of the precursor with cell membranes, in a manner similar to the function of the hydrophobic domain of membrane-bound proteins (e.g., glycophorin). The hydrophobic extra piece apparently directs most precursor molecules to the endoplasmic reticulum, where they are cleaved to yield mature L chain destined for secretion; a few precursor molecules escape cleavage and are embedded in the cell surface to serve as the antigen-recognizing receptor. The probability that the Leu-Leu-Leu-Trp-Val sequence occurs by chance is 1.6 .times. 10-8. Duplication of a short DNA segment apparently occurs in the structural gene coding for the MOPC-321 precursor. Duplication with inversion is indicated from inverted repetition of the Phe-Leu-Leu sequence in the extra piece of MOPC-41 precursor.This publication has 25 references indexed in Scilit:
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