ABCMdb

ABCC7 p.Asp979Arg

None has been submitted yet.

Publications

PMID: 11118444 [PubMed] Clain J et al: "Two mild cystic fibrosis-associated mutations result in severe cystic fibrosis when combined in cis and reveal a residue important for cystic fibrosis transmembrane conductance regulator processing and function."

No. Sentence Comment

72 Asp-979 was changed to Val (small hydrophobic residue; D979V), Arg (positively charged residue; D979R), or Glu (negatively charged residue; D979E). Login to comment
73 D979V (also a naturally occurring mutant) and D979R had impaired processing FIG. 1. Login to comment
101 Charge-reversal Mutants-Taking into account the functional defects that result when Arg-347 and Asp-979 are each replaced with an uncharged amino acid such as His (uncharged at pH 7.3) and Ala (R347H and D979A), we constructed additional mutants with different charge combinations at residues 347 and 979, including the R347D-D979R double mutant in which the positive and negative charges were swapped. Login to comment
118 essing of D979R, R347H-D979R, and R347D-D979R was differently impaired (Fig. 3; gray bars). Login to comment
120 This suggests that 347 residue could interact directly or indirectly with Arg-979 (D979R). Login to comment
121 Whole-cell measurements indicated that D979R resulted in a much greater decrease in chloride current (4.5 Ϯ 2.4 pA/pF; n ϭ 6) than D979A (Fig. 2D), although both proteins were processed similarly. Login to comment
123 The Cl- current of R347D-D979R (2.8 Ϯ 1.7 pA/pF; n ϭ 9) was not significantly different from those of D979R and R347H-D979A (Fig. 2D). Login to comment
124 This result is consistent with the poor amount of R347D-D979R protein at the cell surface. Login to comment
134 Our data strongly suggest that mutation D979R alters the properties of the chloride channel, and mutational analysis of 979 residue also confirmed that the requirements for channel processing and function are different, consistent with data for other residues (17, 18, 21). Login to comment
143 First, several lines of experimental evidence indicate that there is probably no direct salt bridge between Arg-347 and Asp-979: (i) removal of either the positive charge at position 347 (R347H and R347D) or the negative charge at position 979 (D979A, D979V, and D979R) has different effects on CFTR processing; (ii) the double-neutral (R347H-D979A) and reversed-charged (R347D-D979R) replacements for Arg-347 and Asp-979 do not lead to the recovery of wild-type processing. Login to comment
146 This is supported by the decrease in the processing efficiency of D979R mutants combined with positive, neutral, and negative charges at residue 347. Login to comment