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Structural arrangement of the transmission interface in the antigen ABC transport complex TAP resolved
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 experimental data and the homology to the bacterial ABC exporter Sav1866, a team of scientists from the Goethe University Frankfurt and the University of Calgary 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 crosslinking
approaches.
In a research paper in the Proceedings of the National Academy of Sciences of the USA (published online ahead of print on 19 March 2009) they demonstrate the functional importance of the newly identified X-loop in the NBD in coupling substrate binding to downstream events in the transport cycle. They verified domain swapping in a heterodimeric ABC halftransporter complex by cysteine cross-linking. Either substrate binding or translocation can be blocked by cross-linking the X-loop to coupling helix 2 or 1, respectively.
Their 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.
[Further information about the research of Robert Tampé's group]