ABCMdb

ABCB3 p.Glu602Ala

Predicted by SNAP2:	A: D (71%), C: D (75%), D: N (61%), F: D (85%), G: D (85%), H: D (75%), I: D (80%), K: D (91%), L: D (85%), M: D (80%), N: D (85%), P: D (91%), Q: D (71%), R: D (91%), S: D (85%), T: D (85%), V: D (75%), W: D (85%), Y: D (85%),
Predicted by PROVEAN:	A: D, C: D, D: N, 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, W: D, Y: D,

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Publications
[hide] Structural arrangement of the transmission interfa... Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5551-6. Epub 2009 Mar 18. Oancea G, O'Mara ML, Bennett WF, Tieleman DP, Abele R, Tampe R
Structural arrangement of the transmission interface in the antigen ABC transport complex TAP.
Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5551-6. Epub 2009 Mar 18., [PMID:19297616]

Abstract [show]
The transporter associated with antigen processing (TAP) represents a focal point in the immune recognition of virally or malignantly transformed cells by translocating proteasomal degradation products into the endoplasmic reticulum-lumen for loading of MHC class I molecules. Based on a number of experimental data and the homology to the bacterial ABC exporter Sav1866, we constructed a 3D structural model of the core TAP complex and used it to examine the interface between the transmembrane and nucleotide-binding domains (NBD) by cysteine-scanning and cross-linking approaches. Herein, we demonstrate the functional importance of the newly identified X-loop in the NBD in coupling substrate binding to downstream events in the transport cycle. We further verified domain swapping in a heterodimeric ABC half-transporter complex by cysteine cross-linking. Strikingly, either substrate binding or translocation can be blocked by cross-linking the X-loop to coupling helix 2 or 1, respectively. These results resolve the structural arrangement of the transmission interface and point to different functions of the cytosolic loops and coupling helices in substrate binding, signaling, and transport.

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Sentences [show]
No. Sentence Comment
57 Remarkably, the X-loop mutations showed a reduced transport activity, with 50% transport activity for E602C and 20% for E602D or E602A (Fig. 2B). Login to comment
58 Complete disruption of peptide transport was observed for the E602R mutant. Login to comment