ABCMdb

PMID: 22973227

Patrick AE, Thomas PJ
Development of CFTR Structure.
Front Pharmacol. 2012 Sep 6;3:162. doi: 10.3389/fphar.2012.00162. eCollection 2012., [PubMed]

Sentences

No. Mutations Sentence Comment

85 ABCC7 p.Arg1070Trp Notably, the W277 position is equivalent to the R1070 position in ICL4 (Mornon et al., 2008) that when mutated, R1070W, suppresses the ࢞F508 mutation (Thibodeau et al., 2010; Mendoza et al., 2012). Login to comment 155 ABCC7 p.Leu1065Pro ABCC7 p.Arg1066Cys ABCC7 p.Ala1067Thr For instance, in the NBD-ICL4 interface, mutants in ICL4 including L1065P, R1066C, and A1067T alter trafficking and chloride channel function (Cotten et al., 1996; Seibert et al., 1996). Login to comment 160 ABCC7 p.Gly85Glu ABCC7 p.Gly91Arg An example of mutants similarly located within CFTR with different local mechanisms of misfolding are the G85E and G91R mutations. Login to comment 163 ABCC7 p.Gly85Glu Recently, G85E was found to dramatically alter the conformation/integration profile of TM1 (Patrick et al., 2011). Login to comment 165 ABCC7 p.Gly91Arg The G91R mutant was predicted to have a similar effect on CFTR (Xiong et al., 1997), but this proved not to be true with regards to the TM1 conformation/integration profile (Patrick et al., 2011). Login to comment 166 ABCC7 p.Gly85Glu ABCC7 p.Gly91Arg Interestingly, the corrector compound four rescues G91R but not G85E-CFTR (Grove et al., 2009), suggesting the differences in the mutant molecular pathologies may be relevant for their ability to benefit from specific treatments to rescue defective CFTR. Login to comment 202 ABCC7 p.Gly551Asp Thus far, great success has occurred in rescuing the CF-causing G551D mutant. Login to comment 203 ABCC7 p.Gly551Asp G551D-CFTR has normal cell surface expression and half-life, but confers a severe defect in channel gating (Welsh and Smith, 1993). Login to comment 205 ABCC7 p.Gly551Asp This compound has since undergone clinical trials showing efficacy in CF patients (Accurso et al., 2010; Ramsey et al., 2011), has been approved by the FDA for treatment of G551D based CF in patients over 6 years old, and is now marketed as Kalydecoࡊ. Login to comment