ABCC7 p.Thr1396Ala
| Predicted by SNAP2: | A: D (63%), C: N (61%), D: D (75%), E: D (80%), F: D (80%), G: D (71%), H: D (66%), I: D (66%), K: D (85%), L: D (75%), M: D (66%), N: D (66%), P: D (71%), Q: D (75%), R: D (80%), S: D (59%), V: D (66%), W: D (85%), Y: D (80%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, V: D, W: D, Y: D, |
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[hide] Aggregation of misfolded proteins can be a selecti... J Biol Chem. 2002 Sep 13;277(37):34462-70. Epub 2002 Jun 25. Milewski MI, Mickle JE, Forrest JK, Stanton BA, Cutting GR
Aggregation of misfolded proteins can be a selective process dependent upon peptide composition.
J Biol Chem. 2002 Sep 13;277(37):34462-70. Epub 2002 Jun 25., 2002-09-13 [PMID:12084728]
Abstract [show]
Intracellular aggregation of misfolded proteins is observed in a number of human diseases, in particular, neurologic disorders in which expanded tracts of polyglutamine residues play a central role. A variety of other proteins are prone to aggregation when mutated, indicating that this process is a common pathologic mechanism for inherited disorders. However, little is known about the relationship between the sequence of aggregating peptides and the specificity of intracellular accumulation. Here we demonstrate that substitution of two residues eliminates aggregation of a 111-amino acid peptide derived from the C-terminal portion of the cystic fibrosis transmembrane conductance regulator (CFTR). We also show that fusion to a reporter protein considerably alters the subcellular distribution of aggregating peptide. When fused to green fluorescent protein, the peptide containing amino acids 1370-1480 of CFTR accumulates in large perinuclear or nuclear aggregates. The same CFTR fragment devoid of green fluorescent protein localizes predominantly to discrete accumulations associated with mitochondria. Importantly, both types of accumulation are dependent on the presence of the same two amino acids within the CFTR sequence. Co-expression studies show that both CFTR-derived proteins can co-localize in large cytoplasmic/nuclear aggregates. However, neither CFTR construct accumulates in intracellular inclusions formed by N-terminal fragment of huntingtin. In addition to unique accumulation patterns, each aggregating peptide shows differences in association with chaperone proteins. Thus, our results indicate that the process of intracellular aggregation can be a selective process determined by the composition of the aggregating peptides.
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No. Sentence Comment
88 The replacement of Thr-1396 with alanine had no effect on aggregation of the GFP-tagged protein (Fig. 1D).
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ABCC7 p.Thr1396Ala 12084728:88:19
status: NEW108 B-E, the effect of different mutations within the ag region, including ⌬ag (B), V1397E (C), T1396A (D), and double mutation H1402A,R1403A (E) on the aggregation of C terminus of CFTR fused to GFP (shown in green) in transiently transfected human airway epithelial (IB3-1) cells.
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ABCC7 p.Thr1396Ala 12084728:108:99
status: NEW