ABCC7 p.Arg1070Ala
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PMID: 20590134
[PubMed]
Loo TW et al: "The V510D suppressor mutation stabilizes DeltaF508-CFTR at the cell surface."
No.
Sentence
Comment
5
It was also observed that introduction of the V510R/ R1070D mutations into ΔF508-CFTR also promoted maturation whereas the V510D/R1070A mutations did not.
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ABCC7 p.Arg1070Ala 20590134:5:135
status: NEW80 We tested the contribution of Arg1070 by introducing the R1070A change intoΔF508/V510D.
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ABCC7 p.Arg1070Ala 20590134:80:57
status: NEW81 Asshownin Figure 4A, mature protein was not detectable in mutant ΔF508/ V510D/R1070A.
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ABCC7 p.Arg1070Ala 20590134:81:84
status: NEW82 To test if the R1070A mutation alone affected maturation of ΔF508, mutants ΔF508/R1070A and ΔF508 were expressed at 30 °C.
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ABCC7 p.Arg1070Ala 20590134:82:15
status: NEWX
ABCC7 p.Arg1070Ala 20590134:82:93
status: NEW84 Therefore, it was unlikely that the R1070A mutant caused further misfolding of ΔF508-CFTR.
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ABCC7 p.Arg1070Ala 20590134:84:36
status: NEW85 This is consistent with the observation that introduction of the R1070A mutation into wild-type CFTR also did not affect its maturation (data not shown).
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ABCC7 p.Arg1070Ala 20590134:85:65
status: NEW
PMID: 23378596
[PubMed]
Hunt JF et al: "Cystic fibrosis transmembrane conductance regulator (ABCC7) structure."
No.
Sentence
Comment
256
Moreover, restoration of the trafficking of F508del-NBD1 by the V510D suppressor mutation, which introduces a negative charge into a generally apolar region J.F. Hunt et al. 16 Cite this article as Cold Spring Harb Perspect Med 2012;3:a009514 www.perspectivesinmedicine.org by Cold Spring Harbor Laboratory Press at SEMMELWEIS UNIV OF MEDICINE on December 5, of the interdomain interface (Fig. 4C,D), is strongly attenuated by introducing the R1070A or R1070D mutations that remove a complementary positive charge from the proximal surface of the TMD (Loo et al. 2010).
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ABCC7 p.Arg1070Ala 23378596:256:444
status: NEW
PMID: 23924900
[PubMed]
Ren HY et al: "VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1."
No.
Sentence
Comment
134
To determine whether formation of a salt bridge between D510 and R1070 was important for this effect, we introduced the R1070A mutation into V510D/F508del-CFTR.
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ABCC7 p.Arg1070Ala 23924900:134:120
status: NEW135 In the presence of VX-809, the accumulation of the C-band of R1070A/V510D/ F508del-CFTR was reduced by 75% relative to V510D/F508 -CFTR (Figure 6B, lane 7).
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ABCC7 p.Arg1070Ala 23924900:135:61
status: NEW136 Yet VX-809 was still able to increase folded R1070A/V510D/F508-CFTR to levels that were significantly higher than those for VX-809-treated F508del-CFTR.
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ABCC7 p.Arg1070Ala 23924900:136:45
status: NEW137 Because the V510D mutation can modestly improve the thermodynamic stability of purified NBD1 (Lewis et al., 2010; Wang et al., 2010), the residual VX-809 corrector function on R1070A/V501D/F508del-CFTR could result from thermodynamic stabilization of NBD1 that would occur in the absence of salt-bridge formation between D510 and R1070.
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ABCC7 p.Arg1070Ala 23924900:137:176
status: NEW