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ABC proteins in antigen translocation and viral inhibition

Nature Chemical Biology volume 6, pages 572–580 (2010)Cite this article

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An Erratum to this article was published on 17 September 2010

This article has been updated

Abstract

How ABC transporters work is a key issue because of their important roles in multidrug resistance of pathogenic bacteria, reduced efficacy of antitumor drugs, cholesterol metabolism, cell homeostasis and immune response. In the past few years, significant progress has been made in crystallization and structure determination of (mostly) bacterial ABC transporters, as well as in functional studies on ABC systems involved in human pathology. In this review, we use the transporter associated with antigen processing (TAP) to illustrate what is known regarding the mechanism of substrate transport. We also discuss the chemical basis of substrate recognition by TAP and the allosteric cross-talk between the binding of substrate, the release of chemical energy by ATP hydrolysis and cross-membrane translocation. Finally, we detail the role of TAP in a large macromolecular assembly, which optimally loads MHC class I molecules, and the interference with this machinery by TAP-targeted viral factors. Because of structural and probable mechanistic similarities, the understanding of the detailed structure and mechanism of TAP will be applicable to all ABC systems, including those of medical relevance.

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Figure 1: Structures of ABC transporters classified according to TMD organization.
Figure 2: Function of the TAP complex in antigen processing via MHC class I molecules.
Figure 3: Structural organization of the TAP complex.
Figure 4: Translocation cycle of the TAP complex.
Figure 5: Immune evasion strategies by blocking peptide translocation.

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Change history

  • 17 September 2010

    In the version of this article initially published, four of the ATP molecules in Figure 4a were incorrectly labeled as ADP. The errors have been corrected in the HTML and PDF versions of the article.

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Acknowledgements

The work in R.T.'s lab is supported by the German Research Foundation (SFB 807 – Transport and Communication Across Biological Membranes, TA157/7 and AB149/1) as well as by the European Drug Initiative on Channels and Transporters project, funded by the European Commission Seventh Framework Program.

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  1. Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt, Germany

    David Parcej & Robert Tampé

  2. Center for Membrane Proteomics, Goethe University Frankfurt, Frankfurt, Germany

    Robert Tampé

  3. Cluster of Excellence Frankfurt (CEF) – Macromolecular Complexes, Goethe University Frankfurt, Frankfurt, Germany

    Robert Tampé

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Parcej, D., Tampé, R. ABC proteins in antigen translocation and viral inhibition. Nat Chem Biol 6, 572–580 (2010). https://doi.org/10.1038/nchembio.410

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