ABCC7 p.Val510Glu
| Predicted by SNAP2: | A: N (82%), C: N (72%), D: N (57%), E: N (72%), F: N (72%), G: N (72%), H: N (66%), I: N (93%), K: N (82%), L: N (87%), M: N (87%), N: N (72%), P: N (66%), Q: N (82%), R: N (78%), S: N (72%), T: N (87%), W: D (66%), Y: N (78%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, W: N, Y: N, |
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[hide] The V510D suppressor mutation stabilizes DeltaF508... Biochemistry. 2010 Aug 3;49(30):6352-7. Loo TW, Bartlett MC, Clarke DM
The V510D suppressor mutation stabilizes DeltaF508-CFTR at the cell surface.
Biochemistry. 2010 Aug 3;49(30):6352-7., 2010-08-03 [PMID:20590134]
Abstract [show]
Deletion of Phe508 (DeltaF508) in the first nucleotide-binding domain (NBD1) of CFTR causes cystic fibrosis. The mutation severely reduces the stability and folding of the protein by disrupting interactions between NBD1 and the second transmembrane domain (TMD2). We found that replacement of Val510 with acidic residues (but not neutral or positive residues) promoted maturation of DeltaF508-CFTR with V510D more efficiently than V510E. Promotion of DeltaF508-CFTR maturation did not require NBD2 as introduction of V510D into a DeltaNBD2/DeltaF508-CFTR mutant restored maturation to levels similar to that of full-length protein. The V510D mutation increased the half-life of mature DeltaF508-CFTR at the cell surface by about 5-fold to resemble the half-life of wild-type CFTR. It was also observed that introduction of the V510R/R1070D mutations into DeltaF508-CFTR also promoted maturation whereas the V510D/R1070A mutations did not. We propose that the V510D mutation in NBD1 promotes maturation and stabilizes DeltaF508-CFTR at the cell surface through formation of a salt bridge with Arg1070 in TMD2.
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No. Sentence Comment
2 We found that replacement of Val510 with acidic residues (but not neutral or positive residues) promoted maturation of ΔF508-CFTR with V510D more efficiently than V510E.
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ABCC7 p.Val510Glu 20590134:2:169
status: NEW51 HEK 293 cells weretransfected withthe cDNAof wild-type CFTR (Figure 1E) or mutants ΔF508 (Figure 1, panels E-H), V510D/ΔF508 (Figure 1F), V510E/ΔF508 (Figure 1G), and V510R/ΔF508 (Figure 1H), and whole cell SDS extracts were subjected to immunoblot analysis 18 h after transfection.
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ABCC7 p.Val510Glu 20590134:51:150
status: NEW53 The V510E mutation also promoted maturation, but it was less efficient than the V510D mutation (12% and 35%, respectively) (Figure 1, panels F and G).
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ABCC7 p.Val510Glu 20590134:53:4
status: NEW71 Whole cell extracts of HEK 293 cells expressing full-length wild-type (E) or ΔF508-CFTRs (E-H) or ΔF508-CFTR containing the V510D(F), V510E (G), or V510R mutation (H) were subjected to immunoblot analysis 18 h after transfection.
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ABCC7 p.Val510Glu 20590134:71:146
status: NEW