ABCC7 p.Tyr577Lys
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PMID: 26149808
[PubMed]
Chong PA et al: "Deletion of Phenylalanine 508 in the First Nucleotide-binding Domain of the Cystic Fibrosis Transmembrane Conductance Regulator Increases Conformational Exchange and Inhibits Dimerization."
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Sentence
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218
b, overlay of spectra of Y577K NBD1 èc;RIèc;RE recorded at 1.7 mM (black) and 0.1 mM (red).
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ABCC7 p.Tyr577Lys 26149808:218:25
status: NEW234 Peaks corresponding to the amide groups of Gly-486, Cys-491, Gly-509, and Gly-551 and the Trp-496 indole NঈH, which have the largest concentration-dependent chemical shift perturbations in the WT, become invisible at high concentrations and nearly so at low concentrations for the Y577K NBD1 mutant (Fig. 6b).
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ABCC7 p.Tyr577Lys 26149808:234:287
status: NEW235 Although the effect of Y577K on the amount of dimer is unclear from these experiments, this mutation in the dimer interface has a pronounced effect (i.e. extensive broadening) on Gly-486, Cys-491, Trp-496, and Gly-509 confirming that it is reasonable to interpret the concentration-dependent chemical shift perturbations at these residues in the WT as a response to dimerization at the expected interface.
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ABCC7 p.Tyr577Lys 26149808:235:23
status: NEW239 Combined with observations seen in Y577K, these data indicate that chemical shift perturbations at Ser-485, Gly-486, Cys-491, Trp-496, and Gly-509 are linked to changes at the presumed heterodimer interface.
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ABCC7 p.Tyr577Lys 26149808:239:35
status: NEW268 Mutations at the dimer interface (Y577K and Y577E) also affect the Q-loop segment conformational sampling.
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ABCC7 p.Tyr577Lys 26149808:268:34
status: NEW334 Evidence supporting the connection between dimerization and the Phe-508 position comes from the large concentration-dependent chemical shift change of the adjacent residue Gly-509 (b03;30 Hz) seen in WT spectra (Fig. 6a) and the concentration-dependent broadening of this signal in the Y577K spectra (Fig. 6b).
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ABCC7 p.Tyr577Lys 26149808:334:289
status: NEW373 Furthermore, mutations in the dimer interface (Y577K and Y577E) clearly alter the Q-loop segment equilibrium, with changes observed as far away from the dimer interface as Gly-509, which is adjacent to the Phe-508 position.
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ABCC7 p.Tyr577Lys 26149808:373:47
status: NEW