ABCC7 p.Trp401Ala
| ClinVar: |
c.1202G>A
,
p.Trp401*
D
, Pathogenic
c.1203G>A , p.Trp401* D , Pathogenic |
| CF databases: |
c.1202G>A or c.1203G>A
,
p.Trp401*
D
, CF-causing
|
| Predicted by SNAP2: | A: D (75%), C: D (71%), D: D (85%), E: D (85%), F: N (53%), G: D (85%), H: D (80%), I: D (75%), K: D (85%), L: D (59%), M: D (75%), N: D (85%), P: D (91%), Q: D (80%), R: D (80%), S: D (85%), T: D (85%), V: D (63%), Y: N (57%), |
| 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, T: D, V: D, Y: D, |
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[hide] Ligand-driven vectorial folding of ribosome-bound ... Mol Cell. 2011 Mar 18;41(6):682-92. Khushoo A, Yang Z, Johnson AE, Skach WR
Ligand-driven vectorial folding of ribosome-bound human CFTR NBD1.
Mol Cell. 2011 Mar 18;41(6):682-92., 2011-03-18 [PMID:21419343]
Abstract [show]
The mechanism by which protein folding is coupled to biosynthesis is a critical, but poorly understood, aspect of protein conformational diseases. Here we use fluorescence resonance energy transfer (FRET) to characterize tertiary structural transitions of nascent polypeptides and show that the first nucleotide-binding domain (NBD1) of human CFTR, whose folding is defective in cystic fibrosis, folds via a cotranslational multistep pathway as it is synthesized on the ribosome. Folding begins abruptly as NBD1 residues 389-500 emerge from the ribosome exit tunnel, initiating compaction of a small, N-terminal alpha/beta-subdomain. Real-time kinetics of synchronized nascent chains revealed that subdomain folding is rapid, occurs coincident with synthesis, and is facilitated by direct ATP binding to the nascent polypeptide. These findings localize the major CF defect late in the NBD1 folding pathway and establish a paradigm wherein a cellular ligand promotes vectorial domain folding by facilitating an energetically favored local peptide conformation.
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No. Sentence Comment
114 In addition, mutations that inhibit ATP binding to NBD1 in full-length CFTR (W401A, A462F, and K464A [Berger et al., 2005]) also inhibited binding to truncated NBD1 (Figures 5E and 5F).
X
ABCC7 p.Trp401Ala 21419343:114:77
status: NEW205 The CFP-NBD1 ATP-binding mutant contained W401A, A462F, and K464A mutations in the ATP-binding site as predicted by the crystal structure (2BBO).
X
ABCC7 p.Trp401Ala 21419343:205:42
status: NEW