Crystal structure and mechanistic basis of a functional homolog of the antigen transporter TAP

Anne Nöll, Christoph Thomas, Valentina Herbring, Tina Zollmann, Katja Barth, Ahmad Reza Mehdipour, Thomas M. Tomasiak, Stefan Brüchert, Benesh Joseph, Rupert Abele, Vincent Oliéric, Meitian Wang, Kay Diederichs, Gerhard Hummer, Robert M. Stroud, Klaas M. Pos, Robert Tampé

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


ABC transporters form one of the largest protein superfamilies in all domains of life, catalyzing the movement of diverse substrates across membranes. In this key position, ABC transporters canmediate multidrug resistance in cancer therapy and their dysfunction is linked to various diseases. Here, we describe the 2.7-Å X-ray structure of heterodimeric Thermus thermophilus multidrug resistance proteins A and B (TmrAB), which not only shares structural homology with the antigen translocation complex TAP, but is also able to restore antigen processing in human TAP-deficient cells. TmrAB exhibits a broad peptide specificity and can concentrate substrates several thousandfold, using only one single active ATP-binding site. In our structure, TmrAB adopts an asymmetric inward-facing state, and we show that the C-terminal helices, arranged in a zipper-like fashion, play a crucial role in guiding the conformational changes associated with substrate transport. In conclusion, TmrAB can be regarded as a model system for asymmetric ABC exporters in general, and for TAP in particular.

Original languageEnglish (US)
Pages (from-to)E438-E447
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
StatePublished - Jan 24 2017
Externally publishedYes


  • ABC transporter
  • Conformational dynamics
  • Membrane proteins
  • Peptide transport
  • Transporter associated with antigen processing

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Crystal structure and mechanistic basis of a functional homolog of the antigen transporter TAP'. Together they form a unique fingerprint.

Cite this