ABCMdb

PMID: 9511935

Bianchet MA, Ko YH, Amzel LM, Pedersen PL
Modeling of nucleotide binding domains of ABC transporter proteins based on a F1-ATPase/recA topology: structural model of the nucleotide binding domains of the cystic fibrosis transmembrane conductance regulator (CFTR).
J Bioenerg Biomembr. 1997 Oct;29(5):503-24., [PubMed]

Sentences

No. Mutations Sentence Comment

33 ABCC7 p.Phe508Cys ABCC7 p.Ile506Val ABCC7 p.Ile507Val Importantly, missense mutations such as F508C, I506V and I507V are benign and do not cause the disease [Kobayashi et al. (1990)]. Login to comment 34 ABCC7 p.Ala455Glu ABCC7 p.Gly458Val Other missense mutations are found in or near the motif GX4GK[T/S], i.e., A455E and G458V. Login to comment 35 ABCC7 p.Gly551Asp Significantly, mutation of G551, (G551D) in motif C (LSXGX[R/ K]) is associated with high chloride levels in sweat, pancreatic insufficiency and variable lungdisease, producing a phenotype very similar to AF508 [Hamosh et al. (1992)]. Login to comment 226 ABCC7 p.Glu504Gln Mutations such as E504Q do cause CF. Login to comment 257 ABCC7 p.Glu504Gln Certainly, the disease causing mutation E504Q, and probably the AI507 and AF508 mutations have an effect on the function, position, and in the geometry of the loop that contains E504. Login to comment 263 ABCC7 p.Gly551Asp The G551D mutation, which occurs in this region, may have charge and steric conflicts with E504 which account for the effects of the mutation. Login to comment 264 ABCC7 p.Gly551Asp It is also possible that the G551D mutation impairs critical NBD1 interactions with other CFTR domains. Login to comment 311 ABCC7 p.Gly551Asp However, the G-protein based model suggests a direct explanation for why the mutation G551D, in the core of motif C, affects the ATP binding function. Login to comment 360 ABCC7 p.Pro574His ABCC7 p.Ala455Glu ABCC7 p.Arg560Thr ABCC7 p.Arg553Gln ABCC7 p.Tyr563Asn ABCC7 p.Leu558Ser ABCC7 p.Gly480Cys ABCC7 p.Ser492Phe ABCC7 p.Ala559Thr ABCC7 p.Gly458Val ABCC7 p.Glu504Gln The CFTR NBD1 model that results (Fig. 6) gathers the disease causing mutations in three different clusters: (1) mutations affecting the nucleotide binding pocket and the putative general base: A455E, G458V, E504Q AI507 AF508 P574H; (2) mutations in motif C which are probably related to an interaction with region D: S549[R,N,I] G551[S,D], R553Q; and (3) mutations within or near motif B, L558S, A559T, R560T, Y563N and mutations S492F and G480C. Login to comment