The hydrophobic-staple motif and a role for loop-residues in alpha-helix stability and protein folding

Abstract

A recurrent local structural motif is described at the amino terminus of alpha-helices, that consists of a specific hydrophobic interaction between a residue located before the N-cap, with a residue within the helix (i,i+5 interaction). NMR and CD analysis of designed peptides demonstrate its presence in aqueous solution, its contribution to alpha-helix stability and its role in defining the alpha-helix N terminus limit. Comparison between the N-terminal structures of the peptide and those in proteins with the same fingerprint sequence, shows striking similarities. The change in the polypeptide chain direction produced by the motif suggests an important role in protein folding for residues located in polypeptide segments between secondary structure elements.