PROTEIN secondary structures have been viewed as fundamental building
blocks for protein folding, structure and design. Previous studies ind
icate that the propensities of individual amino acids to form particul
ar secondary structures are the result of a combination of local confo
rmational preferences(1,2) and non-local factors(3-7). To examine the
extent to which non-local factors influence the formation of secondary
structural elements, we have designed an 11-amino-acid sequence (dubb
ed the 'chameleon' sequence) that folds as an alpha-helix when in one
position but as a beta-sheet when in another position of the primary s
equence of the IgG-binding domain of protein G (GB1). Both proteins, c
hameleon-alpha and chameleon-beta, are folded into structures similar
to native GB1, as judged hy several biophysical criteria. Our results
demonstrate that non-local interactions can determine the secondary st
ructure of peptide sequences of substantial length. They also support
views of protein folding that favour tertiary interactions as dominant
determinants of structure (for example, see refs 8,9).