Structural arrangement of the transmission interface in the antigen ABC transport complex TAP

Oancea, Giani, O'Mara, Megan L., Bennett, W. F. Drew, Tieleman, D. Peter, Abele, Rupert and Tampé, Robert (2009) Structural arrangement of the transmission interface in the antigen ABC transport complex TAP. National Academy of Sciences. Proceedings, 106 14: 5551-5556. doi:10.1073/pnas.0811260106


Author Oancea, Giani
O'Mara, Megan L.
Bennett, W. F. Drew
Tieleman, D. Peter
Abele, Rupert
Tampé, Robert
Title Structural arrangement of the transmission interface in the antigen ABC transport complex TAP
Journal name National Academy of Sciences. Proceedings   Check publisher's open access policy
ISSN 0027-8424
Publication date 2009-04-01
Sub-type Article (original research)
DOI 10.1073/pnas.0811260106
Open Access Status Not yet assessed
Volume 106
Issue 14
Start page 5551
End page 5556
Total pages 6
Place of publication United States
Publisher National Academy of Sciences
Language eng
Subject 06 Biological Sciences
03 Chemical Sciences
Abstract 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.
Keyword membrane protein structure
traffic ATPase
substrate recognition
conformational change
cysteine cross-linking
Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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Created: Mon, 27 Sep 2010, 19:48:19 EST by Laura McTaggart on behalf of Faculty of Science