ABCMdb

ABCC7 p.Ala534Pro

None has been submitted yet.

Publications

PMID: 22406676 [PubMed] Aleksandrov AA et al: "Allosteric modulation balances thermodynamic stability and restores function of DeltaF508 CFTR."

No. Sentence Comment

112 Combination of introduction of a proline into the Q-loop at position 492 together with I539T to generate ΔF/PT was sufficient to allow a high level of maturation even without further addition of the substitutions in the I539 loop (A534P) to generate ΔF/2PT or also in the RI (S422P and S434P) to generate ΔF/4PT. Login to comment
121 With the inclusion of S492P± A534P (ΔF/PT or ΔF/ 2PT), the turnover rates were indistinguishable from WT with a T1/2 of ~14 h. When prolines also replaced residues 422 and 434 in the RI to form ΔF/ 4PT, the rate appeared even slower than WT with a T1/2 of ~16 h. Thus, the biological stability of the Fig. 5. Login to comment
128 (c) Western blot of WT and ΔF508 CFTR expressed in HEK-293 cells and ΔF508 modified with I539T (ΔF/T), S422P/S434P/S492P/A534P (ΔF/4P), I539T/S492P (ΔF/PT), I539T/S492P/A534P (ΔF/2PT), and I539T/S422P/S434P/S492P/A534P (ΔF/4PT). Login to comment
136 Thermostable binding of the nucleotide by the WT, which is lost in ΔF508 CFTR,19 was not restored after rescue in cells grown at 27 °C [(r)ΔF panel], but was to some extent by I539T (ΔF/T panel), to a greater extent when S492P was added (ΔF/PT panel), still further with A534P also added (ΔF/2PT panel), and to near the WT level with proline replacements at residues S492 and A534 as well (ΔF/4PT panel). Login to comment
178 HEK293 cells were transiently transfected with Cys-less CFTR or Cys-less ΔF508-CFTR in the presence or absence of the 4PT mutations (S422P/S434P/S492P/A534P/I539T), with the Cys pair V510C/G1069C introduced at the CL4/NBD1 interface. Login to comment

PMID: 23104983 [PubMed] He L et al: "Correctors of DeltaF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein."

No. Sentence Comment

122 4PT, S422P/S434P/S492P/ A534P/I539T. Login to comment
148 A) èc;F508 with NBD1-stabilizing mutations: 4S, I539T/G550E/R553M/R555K; èc;RI, deletion of amino acid residues 404-435; 4PT, S422P/S434P/S492P/A534P/I539T. Login to comment

PMID: 25083918 [PubMed] He L et al: "Restoration of NBD1 thermal stability is necessary and sufficient to correct F508 CFTR folding and assembly."

No. Sentence Comment

45 2PT, S492P/A534P/I539T; 4PT, 2PT + S422P/S434P; 3SS, G550E/R553M/R555K; 4SS, 3SS + I539T; ƊRI, deletion of RI amino acids 404-435; combo, ƊRI + 2PT + 3SS. Login to comment
72 2PT, S492P/ A534P/I539T; 3PT, 2PT + S495P. Login to comment
96 The S492P and I539T substitutions had additive affects such that ƊTm increased to 4.4 &#b0;C, and ƊTm was further increased to 8.4 &#b0;C when the additional mutations A534P/G550E/R553M/R555K were introduced. Login to comment
123 Figure 3e shows that both BIA and BEIA further strongly increased maturation of the NBD1 stabilized variant ƊF508/2PT (S492P/A534P/I539T). Login to comment

PMID: 26384709 [PubMed] Aleksandrov LA et al: "Thermal stability of purified and reconstituted CFTR in a locked open channel conformation."

No. Sentence Comment

20 Abbreviations used: CFTR, cystic fibrosis transmembrane conductance regulator; ABC, ATP-binding cassette; NBD1, N-terminal nucleotide-binding domain; CF, cystic fibrosis; CHO, Chinese hamster ovary; HEK, human embryonic kidney; BHK, baby hamster kidney; Tm, melting temperature; Ti, inactivation temperature; RI, Regulatory Insertion (residues 404-435); 2PT, variant with NBD1 mutations S492P, A534P and I539T; Q loop, residues contacting the gamma-phosphate of ATP; SDR, structurally divers region; DMNG, Decyl Maltose Neopentyl Glycol; MALS, multi-angle light scattering analysis; DOPE, 1,2-dioleoyl-sn-glycero-3-phosphoethanola mine; DOPC, 1,2-dioleoyl-sn-glycero-3-phosphocholine; DOPS, 1,2-dioleoyl-sn- glycero-3-phospho-L-serine; SUV, small unilamellar vesicles; LMV, large multilamellar vesicles; LULV, large unilamellar vesicles; PKA, protein kinase A; RIPA, radioimmunoprecipitation assay; ER, endoplasmic reticulum; RAMP, gradual increase with constant slope. Login to comment
107 As seen in Fig. 2a the ''2PT" variant with NBD1 mutations S492P, A534P and I539T and the DRI variant, from which the Regulatory Insertion (residues 404-435) was deleted both increased expression levels substantially compared to the wild type. Login to comment
109 Channel open probability was substantially reduced in 2PT due to the introduction of the two prolines into the mobile Q loop (S492P) and SDR (A534P) regions of NBD1 (third tracing). Login to comment

PMID: 26517912 [PubMed] Bose SJ et al: "Exploiting species differences to understand the CFTR Cl- channel."

No. Sentence Comment

120 Hypothesizing that structural differences between human and chicken CFTR account for the thermostability of F508del chicken CFTR, Aleksandrov et al. [41] demonstrated that the F508del revertant I539T and four proline residues at key positions within NBD1 (S422P, S434P, S492P and A534P) were responsible for rescuing the processing, plasma membrane stability and function of human CFTR. Login to comment