ABCMdb

ABCC7 p.Pro205Leu

ClinVar:	c.614C>G , p.Pro205Arg ? , not provided c.613C>T , p.Pro205Ser D , Pathogenic
CF databases:	c.613C>T , p.Pro205Ser D , CF-causing ; CFTR1: This mutation was detected by SSCP analysism followed by direct sequencing. Mutation P205S was found in 3/270 unrelated Spanish CF non-[delta]F508 chromosomes. P205S is associated with haplotype 16/44/13. c.614C>G , p.Pro205Arg (CFTR1) D , c.614C>T , p.Pro205Leu (CFTR1) ? ,
Predicted by SNAP2:	A: D (95%), C: D (95%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (95%), K: D (95%), L: D (95%), M: D (95%), N: D (95%), Q: D (95%), R: D (95%), S: N (53%), T: D (95%), V: D (95%), W: D (95%), Y: D (95%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D,

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Publications
[hide] A protein sequence that can encode native structur... Nat Struct Biol. 2002 May;9(5):381-8. Wigley WC, Corboy MJ, Cutler TD, Thibodeau PH, Oldan J, Lee MG, Rizo J, Hunt JF, Thomas PJ
A protein sequence that can encode native structure by disfavoring alternate conformations.
Nat Struct Biol. 2002 May;9(5):381-8., [PMID:11938353]

Abstract [show]
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.

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Sentences [show]
No. Sentence Comment
41 This alternate conformation is apparently not induced specifically by the Ser residue, because the control peptides (P205G, P205A and P205L) each assume a similar non-native structure under these conditions. Login to comment
42 Consistent with this conclusion, full-length P205L mutant CFTR expressed in cultured cells also misfolds, fails to achieve mature glycosylation and is retained in the ER (W.C.W., M.J.C. and P.J.T., unpublished observations). Login to comment
49 CD spec- troscopy30 evaluated the seconday structure of peptides representing wild type m3, the CF-causing mutant P205S, and control peptides P205G, P205A and P205L solubilized in either micellar SDS (0.5% (w/v) SDS and 5mM phosphate buffer, pH 7.2) or polyfluorinated organic solvents (10% HFIP, 40% TFE and 50% (v/v) H2O). Login to comment
50 The lines used to represent each peptide are wild type m3, dashed red; P205S, dashed blue; P205G, solid green; P205A, solid light purple; and P205L, solid black. Login to comment
72 Constructs are denoted as follows: P, TfR-m3 wt; S, TfR-m3 P205S; and L, TfR-m3 P205L. Login to comment
92 Consistent with the peptide results, the wild type chimera properly integrates better than either the P205S or P205L mutants (Fig. 3b). Login to comment
133 A representative IR spectrum (solid line) of the amide I region is presented for the mutant peptide (P205L). Login to comment
136 b, Wild type and mutant (P205L) peptides were first solubilized in neat TFE at 5 mg ml-1 and then unfolded by rapid dilution (1/10) in the strong denaturant 6 M guanidinium-SCN. Login to comment
142 The symbols used are wild type (filled circle) and P205L (open circle). Login to comment