De novo design, expression, and characterization of Felix: A four-helix bundle protein of native-like sequence

Michael H. Hecht, Jane S. Richardson, David C. Richardson, Richard C. Ogden

Research output: Contribution to journalReview article

380 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)884-891
Number of pages8
JournalScience
Volume249
Issue number4971
DOIs
StatePublished - Jan 1 1990

All Science Journal Classification (ASJC) codes

  • General

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