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- Title
A protein sequence that can encode native structure by disfavoring alternate conformations.
- Authors
Wigley, W Christian; Corboy, Michael J; Cutler, Todd D; Thibodeau, Patrick H; Oldan, Jorge; Lee, Min Goo; Rizo, Josep; Hunt, John F; Thomas, Philip J
- Abstract
The linear sequence of amino acids contains all the necessary information for a protein to fold into its unique three-dimensional structure. Native protein sequences are known to accomplish this by promoting the formation of stable, kinetically accessible structures. Here we describe a Pro residue in the center of the third transmembrane helix of the cystic fibrosis transmembrane conductance regulator that promotes folding by a distinct mechanism: disfavoring the formation of a misfolded structure. The generality of this mechanism is supported by genome-wide transmembrane sequence analyses. Furthermore, the results provide an explanation for the increased frequency of Pro residues in transmembrane alpha-helices. Incorporation by nature of such 'negative folding determinants', aimed at preventing the formation of off-pathway structures, represents an additional mechanism by which folding information is encoded within the evolved sequences of proteins.
- Publication
Nature structural biology, 2002, Vol 9, Issue 5, p381
- ISSN
1072-8368
- Publication type
Journal Article
- DOI
10.1038/nsb784