ABCB2 p.Tyr409Cys
| Predicted by SNAP2: | A: D (63%), C: D (66%), D: D (85%), E: D (85%), F: D (53%), G: D (80%), H: N (57%), I: D (63%), K: D (91%), L: D (53%), M: D (66%), N: D (63%), P: D (91%), Q: D (53%), R: D (71%), S: D (53%), T: D (71%), V: N (61%), W: D (71%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: N, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, |
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[hide] Introduction of the most common cystic fibrosis mu... J Biol Chem. 2002 Aug 2;277(31):27585-8. Epub 2002 Jun 17. Loo TW, Bartlett MC, Clarke DM
Introduction of the most common cystic fibrosis mutation (Delta F508) into human P-glycoprotein disrupts packing of the transmembrane segments.
J Biol Chem. 2002 Aug 2;277(31):27585-8. Epub 2002 Jun 17., [PMID:12070134]
Abstract [show]
The most common mutation in cystic fibrosis (deletion of phenylalanine 508 (DeltaF508) in the cystic fibrosis conductance transmembrane regulator (CFTR) gene) causes defective synthesis of CFTR protein. To understand how this deletion interferes with protein folding, we made the equivalent deletion (DeltaY490) in P-glycoprotein (P-gp). A Cys-less P-gp with cysteines in transmembrane (TM) 4 or TM5 can be cross-linked with a cysteine in TM12. Deleting Tyr(490) in P-gp resulted in an inactive and defectively processed mutant in which no cross-linking between TM4 or TM5 and TM12 was detected. Expression of the DeltaY490 mutant in the presence of a chemical chaperone corrected the processing defect and yielded active P-gp mutants that could be cross-linked between TM4 or TM5 and TM12. Cross-linking between TM4 or TM5 and TM12 was also detected when residues (483)TIAENIRYG(491) in P-gp were replaced with residues (501)TIKENIIFG(509) from CFTR (P-gp/CFTR). Deleting Phe(508) in the P-gp/CFTR chimera, however, caused defective processing of the mutant protein and no detectable cross-linking between TM4 or TM5 and TM12. The processing defect was corrected with a chemical chaperone and yielded active P-gp/CFTR mutant proteins that could be cross-linked. These results show that deletion at residue 490 disrupts packing of the TM segments possibly by affecting interaction between the first nucleotide-binding domain (Tyr(490)) and the first cytoplasmic loop (Glu(184)).
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No. Sentence Comment
92 No cross-linked product was detected with either Y409C or E184C (data not shown).
X
ABCB2 p.Tyr409Cys 12070134:92:49
status: NEW