Prediction of the three-dimensional structure of the leader sequence of pre-kappa light chain, a hexadecapeptide.

Abstract

The 3-dimensional structure of the signal sequence for murine .kappa. light chain was calculated by using conformational energy calculations. These calculations, based on tested and reliable potential energy functions, employ a novel global search technique to identify the lowest energy structures for the hexadecapeptide signal sequence, Glu-Thr-Asp-Thr-(Leu3-Trip-Val)2-Pro-Gly. The core hydrophobic sequence, Leu2-Trp-Val-Leu3, adopts an .alpha.-helical conformation that is terminated by chain reversal conformations for the 4 residues, Trp-Val-Pro-Gly. The amino-terminal 4 residues adopt low energy conformations that are fully compatible with the succeeding .alpha.-helix. The immediately neighboring sequence, Asp-Thr, exists in a single lowest energy double-equatorial conformation, whereas the first 2 residues, Glu-Thr, can adopt a variety of low energy conformations. The calculations arrive at a highly structured and specific model for the conformation of a leader sequence, compatible with recent experimental data.