ABCMdb

ABCC7 p.Trp496Phe

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Publications

PMID: 15619636 [PubMed] Thibodeau PH et al: "Side chain and backbone contributions of Phe508 to CFTR folding."

No. Sentence Comment

36 A tryptophan was also introduced at position 508 to assess the effects of substitution of a larger hydrophobic residue and to act as a spectral probe to track the folding of the NBD both in the wild-type domain and in a mutant background of W496F. Login to comment
38 However, when the F508W mutation was introduced onto the background of W496F, folding of the NBD1 was partially restored and the protein was capable of refolding with higher efficiency (>90% soluble) at 4 °C (Fig.1b). Login to comment
46 How does the isolated NBD accommodate such Temperature (ºC) 4 10 16 22 Fractionalyield 0.0 0.5 1.0 Temperature (ºC) 4 10 16 22 Temperature (ºC) 4 10 16 22 Wild type ∆F508 Wild type ∆F508 ̄ F508A ̄ F508M F508P F508W ͷ F508W W496F Wild type ∆F508 F508Q F508R F508D F508S a b c Figure 1 NBD1 folding efficiency as a function of folding temperature. Login to comment
52 (b) The F508W mutant, the only mutant that deviated markedly from the wild type, was rescued by the introduction of a second missense mutation, W496F. Login to comment
104 The structures of NBD1 proteins also suggest a potential mechanism for the deleterious effects of the F508W substitution,as the phenylalanine side chain, although partially surface-exposed and accessible, interacts with surrounding residues.The nearest atom distances from both Trp496 and Met498 to Phe508 are ~4 Å.The additional physical size of the tryptophan side chain thus may not be accommodated by the local protein structure.However,when a second substitution,W496F,was introduced, the folding of the domain was rescued.Given the close proximity of both residues,theW496F substitution probably resolves a steric clash between the substituted tryptophan at position 508 and other local residues,consistent with the refolded protein reaching a native or near-native-state structure in vitro. Login to comment

PMID: 18463704 [PubMed] Serohijos AW et al: "Diminished self-chaperoning activity of the DeltaF508 mutant of CFTR results in protein misfolding."

No. Sentence Comment

170 Interestingly, Thibodeau et al. found that NBD1F508W , the only F508X mutant with a lower folding efficiency than NBD1DF508 , can be rescued by introducing the compensating mutation W496F, which is exactly in the same loop that contains Q493 and F594 [9]. Login to comment