De Novo Design, Expression, and Characterization of Felix: a Four-Helix Bundle Protein of Native-Like Sequence

• DOI: 10.1126/science.2392678
• Publication Date: 2006-10-05T22:10:14Z
• Authors: Michael H. Hecht; Jane S. Richardson; David C. Richardson; Richard C. Ogden
• Keywords: Antiparallel (mathematics); Helix bundle; Helix (gastropod); Sequence (biology)

The protein Felix was designed de novo to fold into an antiparallel four-helix bundle of specific topology. Its sequence 79 amino acid residues is not homologous any known sequence, but "native-like" in that it nonrepetitive and contains 19 the 20 naturally occurring acids. has been expressed from a synthetic gene cloned Escherichia coli , purified homogeneity. Physical characterization indicates (i) monomeric solution, (ii) predominantly α-helical, (iii) intramolecular disulfide bond linking first fourth helices, (iv) buries its single tryptophan apolar environment probably close proximity with bond. These physical properties rule out several alternative structures indicate indeed folds approximately three-dimensional structure.