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Science 9 April 1999:
Vol. 284. no. 5412, pp. 325 - 327
DOI: 10.1126/science.284.5412.325
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Reports

Evolution of a Protein Fold in Vitro

Matthew H. J. Cordes, 1 Nathan P. Walsh, 1 C. James McKnight, 2 Robert T. Sauer 1*

A "switch" mutant of the Arc repressor homodimer was constructed by interchanging the sequence positions of a hydrophobic core residue, leucine 12, and an adjacent surface polar residue, asparagine 11, in each strand of an intersubunit beta  sheet. The mutant protein adopts a fold in which each beta  strand is replaced by a right-handed helix and side chains in this region undergo significant repacking. The observed structural changes allow the protein to maintain solvent exposure of polar side chains and optimal burial of hydrophobic side chains. These results suggest that new protein folds can evolve from existing folds without drastic or large-scale mutagenesis.

1 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2 Department of Biophysics, Boston University School of Medicine, Boston, MA 02118, USA.
*   To whom correspondence should be addressed. E-mail: bobsauer{at}mit.edu

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