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 α-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.
Original language | English (US) |
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Pages (from-to) | 381-388 |
Number of pages | 8 |
Journal | Nature Structural Biology |
Volume | 9 |
Issue number | 5 |
DOIs | |
State | Published - 2002 |
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Genetics