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Volume 17 (2003), Issue 1, Pages 17-30

Secondary Structure as a Conformational Determinant in Processing of Peptide Precursors at Dibasic Amino Acids

Noureddine Lazar,1 Noureddine Brakch,2 Maï Panchal,1 Paul Cohen,1 and Mohamed Rholam1

1Laboratoire de Biochimie des Signaux Régulateurs Cellulaires et Moléculaires, Université Pierre et Marie Curie, Unité Mixte de Recherches 7631 CNRS, 96, Bd Raspail, 75006 Paris, France
2Division d’Hypertension, CHU Vaudois, CH-1011, Lausanne, Switzerland

Copyright © 2003 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The aim of this work was to establish the functional role of selected secondary structure motifs of peptide hormone precursors in their selective recognition by the corresponding converting endoproteases. The strategy was based on the use of synthetic peptides either reproducing or mimicking the sequences of the cleavage regions of two distinct models; i.e. pro-ocytocin–neurophysin and prosomatostatin. Both prohormones were capable to release their biologically active sequences either by cleavage at a dibasic stretch or by proteolysis at a monobasic site.

Both kinetic and thermodynamic parameters of peptide cleavage by various convertases were measured. They were examined in light of structural data on preferred conformations adopted by these substrates, which were obtained by a combination of spectroscopical techniques including CD, FT-IR and proton NMR. In the case of prosomatostatin, these approaches were in addition paralleled by site-directed mutagenesis experiments.

The wealth of collected data point toward the conclusion that β-turns and/or loops, favored by sequences bearing basic residues, constitute a key feature in the specification of those peptide loci which are proteolytically processed in vivo. They will be discussed with respect of other processing mechanisms where these mechanisms were also shown.