Evidence for beta-turn structure in model peptides reproducing pro-ocytocin/neurophysin proteolytic processing site

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biophysics

Background:

• The common oxytocin/neurophysin precursor undergoes proteolytic cleavage at a LysArg site.
• Understanding the structural organization around cleavage sites is crucial for polypeptide hormone processing.

Purpose of the Study:

• To investigate the structural organization of small peptides mimicking the oxytocin/neurophysin precursor around the LysArg cleavage locus.
• To explore the conformational changes induced by different environments.

Main Methods:

• Circular dichroism (CD) spectroscopy.
• Proton Nuclear Magnetic Resonance ([1H] NMR) spectroscopy, including temperature coefficient and Nuclear Overhauser Effect (NOE) measurements.
• Utilized aqueous solutions, sodium dodecyl sulfate (SDS) micelles, and trifluoroethanol (TFE) to simulate different environments.

Main Results:

• Peptides exhibited random coil conformations in aqueous solutions, as indicated by CD and [1H] NMR.
• In membrane-mimicking environments (SDS or TFE), peptides adopted folded structures.
• CD spectra suggested the formation of various beta-turns in rapid equilibrium.
• [1H] NMR data (NH temperature coefficients and NOEs) confirmed the presence of intramolecular contacts and a folded conformation.

Conclusions:

• The study provides evidence for environment-dependent conformational changes in peptides related to the oxytocin/neurophysin precursor cleavage site.
• The findings support hypotheses regarding the secondary structure organization at proteolytic processing sites of polypeptide hormone precursors.
• These structural insights are relevant for understanding hormone processing and precursor maturation.