Referenced in: none

Automatically associated channels: Kir2.3

Title: A protein sequence that can encode native structure by disfavoring alternate conformations.

Authors: W Christian Wigley, Michael J Corboy, Todd D Cutler, Patrick H Thibodeau, Jorge Oldan, Min Goo Lee, Josep Rizo, John F Hunt, Philip J Thomas

Journal, date & volume: Nat. Struct. Biol., 2002 May , 9, 381-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11938353

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.