ABCC8 p.Ser408Glu
| Predicted by SNAP2: | A: N (87%), C: N (78%), D: D (59%), E: N (53%), F: D (63%), G: N (87%), H: D (53%), I: D (59%), K: D (63%), L: D (59%), M: D (59%), N: N (57%), P: N (66%), Q: D (53%), R: D (63%), T: N (93%), V: N (66%), W: D (66%), Y: D (66%), |
| Predicted by PROVEAN: | A: N, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: N, P: D, Q: D, R: D, T: N, V: D, W: D, Y: D, |
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[hide] Mechanism of restriction of normal and cystic fibr... Am J Respir Cell Mol Biol. 2002 Nov;27(5):628-40. Gaden F, Franqueville L, Hong SS, Legrand V, Figarella C, Boulanger P
Mechanism of restriction of normal and cystic fibrosis transmembrane conductance regulator-deficient human tracheal gland cells to adenovirus infection and ad-mediated gene transfer.
Am J Respir Cell Mol Biol. 2002 Nov;27(5):628-40., [PMID:12397023]
Abstract [show]
CF-KM4 (cystic fibrosis transmebrane conductance regulator-deficient) and MM-39 (healthy) cells, two serous cell lines from submucosal tracheal glands, were found to be poorly susceptible to adenovirus (Ad)5 infection and Ad5-mediated gene transduction. The major limiting steps apparently resided in the primary events of Ad5 interaction, i.e., cell attachment and entry. Both CF-KM4 and MM-39 cells failed to express the Coxsackie-Ad receptor (CAR), and experimental data suggested that alpha[2-->6]-linked sialic acid residues of sialoglycoproteins (SAGP) in CF-KM4 cells, and heparan sulfate glycosaminoglycans (HS-GAG) in MM-39, were used as receptors by Ad5 virions. Ad5 attached to SAGP and HS-GAG receptors via its fiber knob domain, but entered the cells via a penton base- and Arg-Gly-Asp (RGD)-integrin-independent pathway. The block to Ad5-mediated gene transfer in MM-39 and KM4 cells could be overcome by conferring to the vector a novel cell-binding specificity. Thus, Ad5 vectors carrying a stretch of 7-lysine residues genetically inserted at the C-terminus of the fiber knob were found to transduce MM-39 cells with a 10- to 20-fold higher efficiency than the original vectors, but the transduction of CF-KM4 was not significantly improved. Retargeting Ad5 to integrin receptors via RGD peptide ligands, inserted at the extremity of the fiber shaft, resulted in a transducing efficiency of 20- and 50-fold higher in MM-39 and KM4 cells, respectively, compared with Ad5 vectors carrying fibers terminated by their natural knob domain.
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No. Sentence Comment
268 A less pronounced cytotoxic effect was observed in a Ser-to-Glu substitution at position 408 (Table 1).
X
ABCC8 p.Ser408Glu 12397023:268:53
status: NEW272 (A) Control, Ad5LacZ-FiWT carried WT fibers, whereas Ad5LacZ-FiK7 and Ad5LacZ-Fi408K7 carried a stretch of seven lysine residues (K7) in fusion to the C-terminus of the knob domain, and Ad5LacZ-Fi408K7 contained an additional fiber knob mutation (S408E).
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ABCC8 p.Ser408Glu 12397023:272:247
status: NEW