ABCMdb

PMID: 14598388

Liu X, Smith SS, Dawson DC
CFTR: what's it like inside the pore?
J Exp Zool A Comp Exp Biol. 2003 Nov 1;300(1):69-75., 2003-11-01 [PubMed]

Sentences

No. Mutations Sentence Comment

93 ABCC7 p.Arg334Cys No functional impact was observed in wild type CFTR upon exposure to these reagents, but covalent charge changes at position 334 (R334C CFTR) produced charge-dependent effects on macroscopic conductance and the shape of the I-V plot. Login to comment 96 ABCC7 p.Arg334Cys ABCC7 p.Arg334Cys ABCC7 p.Arg334His Summarized in Figure 4 are charge-induced changes in R334C or R334H CFTR conductance that result from alteration of external pH or exposure of oocytes expressing R334C CFTR to charged methanethiosulfonate (MTS) reagents. Login to comment 98 ABCC7 p.Arg334Cys ABCC7 p.Arg334Cys ABCC7 p.Arg334His Acidification of the bath solution of oocytes expressing R334C or R334H CFTR, or modification of R334C CFTR by a positively charged MTS Fig. 4. Login to comment 103 ABCC7 p.Arg334Cys (B) pH titration of R334C. Login to comment 104 ABCC7 p.Arg334His (C) pH titration of R334H. Login to comment 108 ABCC7 p.Arg334Cys ABCC7 p.Arg334Cys ABCC7 p.Arg334His On the other hand, alkalinization of the bath solution of oocytes expressing R334C or R334H CFTR or modification of R334C CFTR by a negatively charged MTS reagent, MTSES (sodium [2-sulfonatoethyl]methanethiosulfonate), decreased the whole cell conductance and enhanced the inward rectification of the shape of the I-V plots. Login to comment 110 ABCC7 p.Arg334Cys MTSET modification of R334C CFTR conductance caused an appropriate doubling in single channel conductance and had no marked effect on the open probability of the channel (Smith et al., 2001). Login to comment 114 ABCC7 p.Thr338Ala ABCC7 p.Thr338Ser ABCC7 p.Thr338Cys T338C CFTR undergoes pH-dependent changes in gCl and I-V shape that are not seen in wild type, T338A or T338S CFTR. Login to comment 115 ABCC7 p.Thr338Cys Preliminary data indicate that the pH induced changes in T338C CFTR conductance are due to a change in the single channel conductance without a concurrent change in the open probability. Login to comment 117 ABCC7 p.Thr338Cys ABCC7 p.Thr338Cys ABCC7 p.Thr338His ABCC7 p.Thr338His Titration of the macroscopic conductance due to T338C and T338H CFTR indicates that positive charges at R334, perhaps at K335, and perhaps elsewhere may cause the pKa of T338C CFTR to become more acidic than in free solution (E7.4) and to render T338H CFTR non-titratable. Login to comment 118 ABCC7 p.Arg334Cys ABCC7 p.Arg334Ala ABCC7 p.Thr338Cys ABCC7 p.Thr338His Changing the charge at position 334 either by modification of R334C/T338H CFTR with polar thiol reactive reagents or by amino acid substitution (R334A/T338C) shifts the titration curve in a direction that was predicted on the basis of a nearby positive charge being able to stabilize a titratable group (Liu et al., 2001). Login to comment 202 ABCC7 p.Thr338Cys CFTR: pH titration and chemical modification indicate that T338C (TM6) lies on the outward-facing, water-accessible surface of the protein. Login to comment