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Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter

Author

Listed:
  • Nina Grossmann

    (Institute of Biochemistry, Biocenter, Goethe-University Frankfurt)

  • Ahmet S. Vakkasoglu

    (Harvard University)

  • Sabine Hulpke

    (Institute of Biochemistry, Biocenter, Goethe-University Frankfurt)

  • Rupert Abele

    (Institute of Biochemistry, Biocenter, Goethe-University Frankfurt)

  • Rachelle Gaudet

    (Harvard University)

  • Robert Tampé

    (Institute of Biochemistry, Biocenter, Goethe-University Frankfurt
    Cluster of Excellence Frankfurt—Macromolecular Complexes, Goethe-University Frankfurt)

Abstract

The ATP-binding cassette (ABC) transporter associated with antigen processing (TAP) participates in immune surveillance by moving proteasomal products into the endoplasmic reticulum (ER) lumen for major histocompatibility complex class I loading and cell surface presentation to cytotoxic T cells. Here we delineate the mechanistic basis for antigen translocation. Notably, TAP works as a molecular diode, translocating peptide substrates against the gradient in a strict unidirectional way. We reveal the importance of the D-loop at the dimer interface of the two nucleotide-binding domains (NBDs) in coupling substrate translocation with ATP hydrolysis and defining transport vectoriality. Substitution of the conserved aspartate, which coordinates the ATP-binding site, decreases NBD dimerization affinity and turns the unidirectional primary active pump into a passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not required for translocation per se, but is essential for both active and unidirectional transport. Our data provide detailed mechanistic insight into how heterodimeric ABC exporters operate.

Suggested Citation

  • Nina Grossmann & Ahmet S. Vakkasoglu & Sabine Hulpke & Rupert Abele & Rachelle Gaudet & Robert Tampé, 2014. "Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6419
    DOI: 10.1038/ncomms6419
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    Cited by:

    1. Mark Nijland & Solène N. Lefebvre & Chancievan Thangaratnarajah & Dirk J. Slotboom, 2024. "Bidirectional ATP-driven transport of cobalamin by the mycobacterial ABC transporter BacA," Nature Communications, Nature, vol. 15(1), pages 1-9, December.

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