ABCC7 p.Leu69Gly
| CF databases: |
c.206T>G
,
p.Leu69Arg
(CFTR1)
?
, The above mutation was identified by SSCP analysis and characterized by direct DNA sequencing. The mutation was not found on 100 non-CF chromosomes.
|
| Predicted by SNAP2: | A: D (63%), C: N (53%), D: D (85%), E: D (80%), F: D (63%), G: D (80%), H: D (75%), I: N (57%), K: D (75%), M: N (53%), N: D (75%), P: D (85%), Q: D (71%), R: D (75%), S: D (71%), T: D (71%), V: N (61%), W: D (75%), Y: D (71%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D, |
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[hide] Cooperative assembly and misfolding of CFTR domain... Mol Biol Cell. 2009 Apr;20(7):1903-15. Epub 2009 Jan 28. Du K, Lukacs GL
Cooperative assembly and misfolding of CFTR domains in vivo.
Mol Biol Cell. 2009 Apr;20(7):1903-15. Epub 2009 Jan 28., [PMID:19176754]
Abstract [show]
The cystic fibrosis transmembrane conductance regulator (CFTR) architecture consists of two membrane spanning domains (MSD1 and -2), two nucleotide binding domains (NBD1 and -2), and a regulatory (R) domain. Several point mutations lead to the channel misprocessing, with limited structural perturbation of the mutant domain. To gain more insight into the basis of CFTR folding defect, the contribution of domain-wise and cooperative domain folding was assessed by determining 1) the minimal domain combination that is recognized as native and can efficiently escape the endoplasmic reticulum (ER) retention and 2) the impact of mutation on the conformational coupling among domains. One-, two-, three-, and most of the four-domain assemblies were retained at the ER. Solubilization mutations, however, rescued the NBD1 processing defect conceivably by thermodynamic stabilization. The smallest folding unit that traversed the secretory pathway was composed of MSD1-NBD1-R-MSD2 as a linear or split polypeptide. Cystic fibrosis-causing missense mutations in the MSD1, NBD1, MSD2, and NBD2 caused conformational defect in multiple domains. We propose that cooperative posttranslational folding is required for domain stabilization and provides a plausible explanation for the global misfolding caused by point mutations dispersed along the full-length CFTR.
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No. Sentence Comment
113 The L57G/L69G mutations decreased the melting temperature of the recombinant (molecular mass ϳ12 kDa) from 52 to 28°C (Pakula et al., 1986).
X
ABCC7 p.Leu69Gly 19176754:113:9
status: NEW121 CD4T- and CD4T-m contain the wt or the mutant (L57C/L69G) repressor, respectively.
X
ABCC7 p.Leu69Gly 19176754:121:68
status: NEW