ABCMdb

PMID: 18215767

Deber CM, Cheung JC, Rath A
Defining the defect in F508 del CFTR: a soluble problem?
Chem Biol. 2008 Jan;15(1):3-4., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Phe494Asn ABCC7 p.Phe494Asn ABCC7 p.Gln637Arg ABCC7 p.Gln637Arg In this issue of Chemistry & Biology, Pissarra et al. (2008) show that partial rescue of the trafficking and gating defects of full-length CFTR occurs in vivo upon recapitulation of the solubilizing F494N/Q637R or F428S/F494N/Q637R substitutions in cis with F508 del. Login to comment 18 ABCC7 p.Arg553Gln ABCC7 p.Gly550Glu ABCC7 p.Arg555Lys The first human F508 del-NBD1 structure obtained carried seven additional mutations, three of which (suppressor mutations G550E, R553Q, and R555K) were known to rescue the F508 del-CFTR defect (Chang et al., 1999; DeCarvalho et al., 2002; Teem et al., 1996). Login to comment 19 ABCC7 p.Phe494Asn ABCC7 p.Phe494Asn ABCC7 p.Gln637Arg ABCC7 p.Gln637Arg Two F508 del-NBD1 structures lacking the suppressor mutations but retaining certain other alterations (F494N/Q637R or F428S/F494N/ Q637R) necessary for protein solubility subsequently became available (Lewis et al., 2005, http://www.pdb.org). Login to comment 23 ABCC7 p.Phe429Ser ABCC7 p.Phe494Asn ABCC7 p.Phe494Asn ABCC7 p.Gln637Arg ABCC7 p.Gln637Arg To address this question, Pissarra et al. (2008) report in this issue on the trafficking in mammalian cell lines of full-length CFTR proteins carrying wt, F508 del, or F508 del with the F494N/Q637R or F429S/F494N/ Q637R replacements. Login to comment 25 ABCC7 p.Phe429Ser ABCC7 p.Phe494Asn ABCC7 p.Gln637Arg Strikingly, the solubilizing mutations, notably the triple mutant F429S/ F494N/Q637R, appeared to promote some N-glycan processing in F508 del CFTR, to produce Band C, along with bands of MW intermediate between those of Band B and Band C, suggesting that these replacements partially rescue the trafficking defect. Login to comment