ABCMdb

ABCC7 p.Ala349Lys

None has been submitted yet.

Publications

PMID: 23083715 [PubMed] El Hiani Y et al: "Tuning of CFTR chloride channel function by location of positive charges within the pore."

No. Sentence Comment

43 After neutralization of this endogenous positive charge by the K95Q mutation, introduction of a positive charge at other sites (by mutagenesis to lysine) caused a significant increase in unitary conductance to between 51 5 1% (in K95Q/A349K; n &#bc; 10) and 77 5 1% (in K95Q/M348K; n &#bc; 12) of WT conductance (Fig. 2, A-C), suggesting that a positive charge located at other positions in the pore can effectively rescue the WT conductance phenotype. Login to comment
55 Additional mutations in a K95Q background to transplant the positive charge to pore-lining positions in TM1 (Q98K) or TM6 (I344K, V345K, M348K, and A349K) partially restored NPPB block (Fig. 3), although in no case was the block as strong as for the WT. Login to comment
56 The rank order of the apparent strength of NPPB block was WT > K95Q/V345K > K95Q/I344K > K95Q/Q98K ~ K95Q/ M348K ~ K95Q/A349K (Fig. 3 B). Login to comment
60 As shown in Fig. 4, block by Pt(NO2)4 2 was significantly strengthened in each of the mutants Q98K, I344K, V345K, M348K, and A349K, as well as in the previously unstudied S341K. Login to comment
61 At 0 mV membrane potential, the apparent Kd for Pt(NO2)4 2 block was in the rank order V345K (3.3 5 0.9 mM, n &#bc; 7) % I344K (4.5 5 0.7 mM, n &#bc; 6) < S341K (26.6 5 1.8 mM, n &#bc; 7) < M348K (80.9 5 7.2 mM, n &#bc; 5) % Q98K (95.4 5 11.0 mM, n &#bc; 6) % A349K (117.4 5 7.7 mM, FIGURE 2 Single-channel conductance is restored by moving the positive charge from K95. Login to comment
74 Blocker voltage dependence was also significantly changed in most mutants, with the effective blocker valence (zd) being significantly increased in M348K and significantly decreased in Q98K, V345K, and A349K (Fig. 4 F). Login to comment
90 However, although a single positive charge is necessary, the addition of a second positive charge to this region of the pore (as in the point mutants Q98K, I344K, V345K, M348K, and A349K) failed to increase conductance above WT levels (Fig. 2), as previously observed for S1141K (8). Login to comment
99 In fact, the addition of a second positive charge in Q98K, I344K, V345K, M348K, and A349K led to a small, but significant, decrease in conductance (Fig. 2 C). Login to comment
105 The weakening of blocker binding seen in K95Q is partially reversed by the second site mutations I344K and V345K, and to a lesser extent Q98K, M348K, and A349K. Login to comment
146 Again this appears to be a relatively nonsite-specific effect of positive charge, since all mutants studied (Q98K, S341K, I344K, V345K, M348K, and A349K) led to significant increase in apparent affinity of Pt(NO2)4 2 block (Fig. 4), as did S1141K (8). Login to comment
158 At its cytoplasmic entrance, the pore is wider (15,22), which may explain the weaker ability of the A349K mutation nearer the cytoplasmic end of the inner vestibule to restore single-channel conductance in a K95Q background (Fig. 2). Login to comment