ABCB2 p.Ser142Ala
| Predicted by SNAP2: | A: N (87%), C: N (78%), D: N (78%), E: N (87%), F: N (82%), G: N (82%), H: N (82%), I: N (78%), K: N (87%), L: N (82%), M: N (82%), N: N (87%), P: N (87%), Q: N (87%), R: N (82%), T: N (93%), V: N (93%), W: D (63%), Y: N (72%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, T: N, V: N, W: N, Y: N, |
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[hide] Functional non-equivalence of ATP-binding cassette... J Biol Chem. 2004 Oct 29;279(44):46073-81. Epub 2004 Aug 17. Chen M, Abele R, Tampe R
Functional non-equivalence of ATP-binding cassette signature motifs in the transporter associated with antigen processing (TAP).
J Biol Chem. 2004 Oct 29;279(44):46073-81. Epub 2004 Aug 17., [PMID:15322097]
Abstract [show]
The transporter associated with antigen processing (TAP) is a key component of the cellular immune system. As a member of the ATP-binding cassette (ABC) superfamily, TAP hydrolyzes ATP to energize the transport of peptides from the cytosol into the lumen of the endoplasmic reticulum. TAP is composed of TAP1 and TAP2, each containing a transmembrane domain and a nucleotide-binding domain (NBD). Here we investigated the role of the ABC signature motif (C-loop) on the functional non-equivalence of the NBDs, which contain a canonical C-loop (LSGGQ) for TAP1 and a degenerate C-loop (LAAGQ) for TAP2. Mutation of the leucine or glycine (LSGGQ) in TAP1 fully abolished peptide transport. However, TAP complexes with equivalent mutations in TAP2 still showed residual peptide transport activity. To elucidate the origin of the asymmetry of the NBDs of TAP, we further examined TAP complexes with exchanged C-loops. Strikingly, the chimera with two canonical C-loops showed the highest transport rate whereas the chimera with two degenerate C-loops had the lowest transport rate, demonstrating that the ABC signature motifs control peptide transport efficiency. All single site mutants and chimeras showed similar activities in peptide or ATP binding, implying that these mutations affect the ATPase activity of TAP. In addition, these results prove that the serine of the C-loop is not essential for TAP function but rather coordinates, together with other residues of the C-loop, the ATP hydrolysis in both nucleotide-binding sites.
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No. Sentence Comment
222 The S142A mutant hydrolyzes ATP with 50% of the activity of wild type GlcV.
X
ABCB2 p.Ser142Ala 15322097:222:4
status: NEW233 The introduction of an alanine at this position seems to strengthen the NBD dimer affinity, because, in contrast to wild type GlcV, transient GlcV dimers of S142A mutants could be detected by gel filtration in the presence of MgATP (38).
X
ABCB2 p.Ser142Ala 15322097:233:157
status: NEW223 The S142A mutant hydrolyzes ATP with 50% of the activity of wild type GlcV.
X
ABCB2 p.Ser142Ala 15322097:223:4
status: NEW234 The introduction of an alanine at this position seems to strengthen the NBD dimer affinity, because, in contrast to wild type GlcV, transient GlcV dimers of S142A mutants could be detected by gel filtration in the presence of MgATP (38).
X
ABCB2 p.Ser142Ala 15322097:234:157
status: NEW