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Structural arrangement of the transmission interface in the antigen ABC transport complex TAP.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2009 Apr 07; Vol. 106 (14), pp. 5551-6. Date of Electronic Publication: 2009 Mar 18. - Publication Year :
- 2009
-
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.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B, Member 2
ATP Binding Cassette Transporter, Subfamily B, Member 3
ATP-Binding Cassette Transporters metabolism
Cross-Linking Reagents
Humans
Models, Molecular
Mutagenesis
Protein Binding
Protein Structure, Tertiary
ATP-Binding Cassette Transporters chemistry
Staphylococcus aureus chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 106
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 19297616
- Full Text :
- https://doi.org/10.1073/pnas.0811260106