ABCC7 p.Asp924Val

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PMID: 15798900 [PubMed] Sadlish H et al: "Biogenesis of CFTR and other polytopic membrane proteins: new roles for the ribosome-translocon complex."
No. Sentence Comment
166 Interestingly, removal of a single charged residue from TM8 (D924V) prevented Asn908 from being glycosylated and at the same time conferred TM7-independent stop transfer activity onto the TM8 hydrophobic segment (Carveth et al., 2002).
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ABCC7 p.Asp924Val 15798900:166:61
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183 Similarly, the D924V mutation converts TM8 to a strong, independent stop transfer sequence but dramatically decreases CFTR chloride conductance (D. Dawson and W. Skach, unpublished observations).
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ABCC7 p.Asp924Val 15798900:183:15
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PMID: 19019984 [PubMed] Pitonzo D et al: "Sequence-specific retention and regulated integration of a nascent membrane protein by the endoplasmic reticulum Sec61 translocon."
No. Sentence Comment
43 MATERIALS AND METHODS Plasmid Construction CFTR expression plasmids encoding wild-type and D924V mutant have been described previously (Carveth et al., 2002) and encode a methionine ATG translation start codon followed by CFTR residues Glu838 to Tryp1204.
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ABCC7 p.Asp924Val 19019984:43:91
status: NEW
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46 Mutants encoding D924E, D924R, and A923D/D924V as well as glycosylation mutants were generated by standard techniques using PCR overlap extension as described previously (Carveth et al., 2002) using the following sense (and corresponding antisense) oligonucleotides: GGGGCTAGCACTCATAGTAGAAATA- ACAG(N894A), CATTCTAGAGCGAACAGCTATGCAGTGATTAT(N900A), and GACAAAGGGGCTAGCACTCATTCTAGAGCGAAC(N894A/N900A).
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ABCC7 p.Asp924Val 19019984:46:41
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219 In both wild-type (WT) and D924V mutants, TM8 photocross-links were observed during initial stages of translocon insertion at truncations 957 and 967 (Figure 8).
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ABCC7 p.Asp924Val 19019984:219:27
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220 However, photoadducts to D924V decreased abruptly at truncation sites beyond residue 967 (Figure 8B), and no peptidyl-tRNA-independent photocross-links to residue 913 were observed (Figure 8A).
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ABCC7 p.Asp924Val 19019984:220:25
status: NEW
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221 Thus, the D924V mutant leaves the proximity of Sec61 at an earlier stage of synthesis than its wild-type counterpart and fails to exhibit peptidyl-tRNA-independent TM8-Sec61␣ interactions.
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ABCC7 p.Asp924Val 19019984:221:10
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226 We therefore moved the aspartate group 1 residue toward the N terminus to position 923 (A923D and D924V), which would be located at approxi- Figure 8.
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ABCC7 p.Asp924Val 19019984:226:98
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228 (A) Photocross-linking to integration intermediates (residues 837-977) containing WT and mutant (D924V) TM8 revealed similar UV-dependent photoadducts (upward arrowheads) for truncations 957 and 967 that disappeared after puromycin treatment.
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ABCC7 p.Asp924Val 19019984:228:97
status: NEW
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230 At truncations 977 and 987, photoadducts to WT TM8 increased in intensity and were peptidyl-tRNA independent (lanes 14 and 15 and 20 and 21), whereas photoadducts were absent for the D924V mutant (lanes 17, 18, 23, and 24).
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ABCC7 p.Asp924Val 19019984:230:183
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231 (B) Immunoprecipitation of photoadducts with Sec 61␣ antisera confirmed that the D924V mutation decreases Sec61␣ cross-linking at the same stage of synthesis when photocross-linking to WT TM8 becomes independent of the peptidyl-tRNA bond.
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ABCC7 p.Asp924Val 19019984:231:88
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255 A923D, D924V mutations decreased Sec61␣ photocross-linking (to residue 913) after puromycin treatment (compare lane 4 with lane 10) but significantly increased the peptidyl-tRNA-independent photocross-linking to residue 912 (lanes 2 and 8).
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ABCC7 p.Asp924Val 19019984:255:7
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283 Moreover, translocation termination is accomplished by both WT TM8 and the D924V mutant (Carveth et al., 2002), but integration is delayed only when an acidic residue is present.
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ABCC7 p.Asp924Val 19019984:283:75
status: NEW
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PMID: 23248597 [PubMed] Kim SJ et al: "Mechanisms of CFTR Folding at the Endoplasmic Reticulum."
No. Sentence Comment
100 Interestingly, removal of an aspartate residue from TM8 (D924V) prevents transient lumenal exposure and at the same time confers independent stop transfer activity.
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ABCC7 p.Asp924Val 23248597:100:57
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111 Similarly, the D924V mutation converts TM8 to a strong strop transfer sequence and facilitates cotranslational membrane integration, but decreases CFTR chloride conductance (our observations).
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ABCC7 p.Asp924Val 23248597:111:15
status: NEW
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