Experimental analysis of the Schellman motif

Area of Science:

• * Protein structure and bioinformatics
• * Biophysical chemistry

Background:

• * A specific sequence fingerprint (Gly at i, hydrophobic at i+1 and i-4, polar/Ala at i-2) is overrepresented at alpha-helix C-termini.
• * This fingerprint is often linked to the Schellman motif, involving hydrophobic side-chain interactions.

Purpose of the Study:

• * To investigate the role of this hydrophobic interaction in helix stability and Schellman motif formation.
• * To assess the formation propensity of this motif in aqueous solution versus organic co-solvents.

Main Methods:

• * Statistical analysis of protein databases.
• * Nuclear Magnetic Resonance (NMR) spectroscopy.
• * Far-UV Circular Dichroism (CD) spectroscopy on polyalanine-based peptides.

Main Results:

• * The studied motif is poorly populated in aqueous solution and minimally contributes to alpha-helix stability.
• * Hydrophobic interactions within the fingerprint are not formed in water but readily occur in 30% trifluoroethanol.
• * This suggests no intrinsic sequence or steric hindrance to formation in aqueous solution.

Conclusions:

• * The C-terminal helix motif, despite its prevalence, has a limited role in helix stability in water.
• * Its formation may be influenced by environmental factors or selected for three-dimensional packing rather than stability.
• * This motif serves as an example of local interactions driven by packing and potentially environmental selection.