ABCMdb

PMID: 1699669

Cheng SH, Gregory RJ, Marshall J, Paul S, Souza DW, White GA, O'Riordan CR, Smith AE
Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis.
Cell. 1990 Nov 16;63(4):827-34., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC7 p.Lys464Met Examination of the various mutant proteins in COS-7 cells indicated that mature, fully glycosylated CFTR was absent from cells containing AF508, Al507, K464M, F506R, and S5491 cDNA plasmids. Login to comment 112 ABCC7 p.Lys1250Met We also made the equivalent mutation within the second nucleotide binding domain (K1250M), and we changed to glutamine both asparagine residues (at 894 and 900) to which carbohydrate is predicted to be attached (N894,900Q) (Riordan et al., 1989). Login to comment 117 ABCC7 p.Lys464Met ABCC7 p.Lys1250Met Analysis of Mutant Forms of CFTR Expression vectors containing wild-type CFTR (pMT-CFTR, lane 2) and those containing the mutants pMT-CFTR-K464M (lane 3) pMT-CFTR-K1250M (lane 4) pMT-CFTR-Al507 (lane 5) pMT-CFTR-N894. Login to comment 119 ABCC7 p.Arg334Trp ), and pMT-CFTR- R334W (lane 7) were transfected into COS-7 cells. Login to comment 124 ABCC7 p.Lys464Met K464M cDNA transfected cells, like their Al507 and AF508 nucleotide binding domain 1 mutant counterparts, contain no band C (lane 3). Login to comment 127 ABCC7 p.Arg334Trp The mutation R334W does not prevent maturation of recombinant CFTR band C (lane 7). Login to comment 128 ABCC7 p.Gly551Asp Table 1 summarizes data obtained with all the mutants including two other naturally occurring CF-associated mutations S549l and G551D. Login to comment 130 ABCC7 p.Phe508Arg Also included is F508R, in which we changed the residue at 508 rather than deleting it. Login to comment 131 ABCC7 p.Gly551Asp Interestingly, the results using these mutants show S5491 CFTR does not mature but G551D does. Login to comment 132 ABCC7 p.Phe508Arg The mutation of phenylalanine 508 to arginine also results in CFTR that does not mature. Login to comment 137 ABCC7 p.Arg334Trp ABCC7 p.Lys464Met ABCC7 p.Lys1250Met ABCC7 p.Phe508Arg CFTR Mutants Mutant CF Exon CFTR Domain A B C Wild type R334W K464M Al507 AF508 F508R s5491 G551 D N894,900Q K1250M Tthllll Y 7 N 9 Y 10 Y 10 N 10 Y 11 Y 11 N 15 N 20 N 22 TM6 NBDl NBDl NBDl NBDl NBDl NBDl ECD4 NBD2 Term - + ++ - + ++ - + - - + - - + - - + - - + - - + ++ + - - - + ++ - + - The known association with CF (Y, yes; N, no), exon localization, domain location, and presence (+ ) or absence (- ) of bands A, B, and C of mutant CFTR species is shown. Login to comment 169 ABCC7 p.Gly551Asp ABCC7 p.Phe508Arg All the mutations around 508 studied here (AF508, Al507, F508R) fail to generate mature CFTR, whereas of mutations at the second site, S549l does not produce mature CFTR but G551D does. Login to comment 177 ABCC7 p.Lys1250Met K484M does not produce mature CFTR, whereas K1250M does. Login to comment 179 ABCC7 p.Lys464Met ABCC7 p.Lys1250Met We need to study the ability of these mutants to complement the chloride channel defect in CF epithelial cells to establish, for example, whether K1250M and K464M both abolish function. Login to comment 181 ABCC7 p.Arg334Trp Mutant R334W (X. Estivill, personal communication) emphasizes the importance of the transmembrane domains in the activity of CFTR. Login to comment 198 ABCC7 p.Gly551Asp ABCC7 p.Arg334Trp Indeed, R334W and G551D have been detected in CF chromosomes and presumably encode inactive CFTR (X. Estivill, personal communication; Kerem et al., 1990). Login to comment