ABCB3 p.Cys362Ala
| Predicted by SNAP2: | A: N (87%), D: N (57%), E: N (72%), F: N (72%), G: N (72%), H: N (78%), I: N (82%), K: N (72%), L: N (72%), M: N (87%), N: N (78%), P: N (61%), Q: N (78%), R: N (66%), S: N (87%), T: N (93%), V: N (82%), W: N (61%), Y: N (72%), |
| Predicted by PROVEAN: | A: N, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: N, T: N, V: N, W: D, Y: D, |
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[hide] Use of Functional Polymorphisms To Elucidate the P... J Immunol. 2015 Oct 1;195(7):3436-48. doi: 10.4049/jimmunol.1500985. Epub 2015 Aug 31. Geng J, Pogozheva ID, Mosberg HI, Raghavan M
Use of Functional Polymorphisms To Elucidate the Peptide Binding Site of TAP Complexes.
J Immunol. 2015 Oct 1;195(7):3436-48. doi: 10.4049/jimmunol.1500985. Epub 2015 Aug 31., [PMID:26324772]
Abstract [show]
TAP1/TAP2 complexes translocate peptides from the cytosol to the endoplasmic reticulum lumen to enable immune surveillance by CD8(+) T cells. Peptide transport is preceded by peptide binding to a cytosol-accessible surface of TAP1/TAP2 complexes, but the location of the TAP peptide-binding pocket remains unknown. Guided by the known contributions of polymorphic TAP variants to peptide selection, we combined homology modeling of TAP with experimental measurements to identify several TAP residues that interact with peptides. Models for peptide-TAP complexes were generated, which indicate bent conformation for peptides. The peptide binding site of TAP is located at the hydrophobic boundary of the cytosolic membrane leaflet, with striking parallels to the glutathione binding site of NaAtm1, a transporter that functions in bacterial heavy metal detoxification. These studies illustrate the conservation of the ligand recognition modes of bacterial and mammalians transporters involved in peptide-guided cellular surveillance.
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No. Sentence Comment
154 To further investigate which cysteine residue within the internal cavity of the wild-type rTAP becomes conjugated with TC6R, two mutant constructs (rTAP1[C273A] and rTAP2a[C362A]) were generated and tested for cross-linking to the TC6R peptide.
X
ABCB3 p.Cys362Ala 26324772:154:172
status: NEW157 In contrast, the rTAP1(C175A)/TAP2a and the rTAP1/TAP2a(C362A) mutants retained the ability to crosslink with the TC6R peptide (Fig. 3D).
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ABCB3 p.Cys362Ala 26324772:157:56
status: NEW213 Top panel, Cross-linking between TC2R or TC6R (1 mM) and wild-type or mutants, rTAP1(C175A)/TAP2a (T1C175A/T2), rTAP1/TAP2a(C362A) (T1/T2C362A), and rTAP1(C273A)/TAP2a (T1C273A/T2).
X
ABCB3 p.Cys362Ala 26324772:213:124
status: NEW227 To avoid cross-linking to other cysteine residues in the vicinity of the cavity, the cysteine mutants were generated on the rTAP1(C273A)/TAP2a(C362A) background (named rTAP1*/TAP2a*) to remove the other cysteines that face the internal cavity of the TAP heterodimer (Fig. 3A).
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ABCB3 p.Cys362Ala 26324772:227:143
status: NEW295 All constructs shown in the figure are on the rTAP1(C273A)/TAP2a(C362A) background (labeled as T1*/T2*).
X
ABCB3 p.Cys362Ala 26324772:295:65
status: NEW