Experimental analysis of the Schellman motif.
Statistical analysis of the protein database indicates that the presence of a particular sequence fingerprint, involving a Gly residue at position i, two hydrophobic residues at positions i + 1 and i-4, and a polar or Ala residue at position i-2, is found at the C-terminal end of alpha-helices 5.9 times more frequently than expected from a random distribution. This particular sequence fingerprint is frequently associated (approximately 50% of the cases) with a local motif known as the Schellman motif. Formation of this motif with the above fingerprint is accompanied by an interaction between the side-chains of the two hydrophobic residues (97% of the cases). To assess the role of this hydrophobic interaction in helix stability and in the formation of the Schellman motif, we have analysed by nuclear magnetic resonance (NMR) and far-UV circular dichroism (CD) a set of polyalanine-based peptides containing the sequence fingerprint described above. Our results show that this motif is not populated to a large extent in aqueous solution and contributes little to alpha-helix stability, the opposite to what has previously been found in two local motifs at the N termini of helices (hydrophobic staple and capping-box). Addition of 30% (v/v) trifluoroethanol results in the formation of the hydrophobic interaction between residues i-4 and i + 1 of the fingerprint, thus showing that there are no sequence or sterical reasons that prevent its formation in aqueous solution. This motif could be an example of a local interaction selected both on a stability basis and because of three-dimensional packing reasons.
Viguera
A R
AR
EMBL, Heidelberg, Germany.
Serrano
L
L
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D018257:Helix-Loop-Helix Motifs; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D013223:Statistics as Topic; D014270:Trifluoroethanol / Q000737:chemistry; D014867:Water
D011506:Proteins; D014867:Water; D014270:Trifluoroethanol