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

Nöll, Anne; Thomas, Christoph; Herbring, Valentina; Zollmann, Tina; Barth, Katja; Mehdipour, Ahmad Reza; Tomasiak, Thomas M.; Diederichs, Kay; Stroud, Robert M.; Tampé, Robert

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

Dateien

Noell_0-398406.pdfGröße: 1.17 MBDownloads: 224

Datum

2017

Autor:innen

Nöll, Anne

Thomas, Christoph

Herbring, Valentina

Zollmann, Tina

Barth, Katja

Mehdipour, Ahmad Reza

Tomasiak, Thomas M.

Diederichs, Kay

Stroud, Robert M.

Tampé, Robert

et al.

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2017, 114(4), pp. E438-E447. ISSN 0027-8424. eISSN 1091-6490. Available under: doi: 10.1073/pnas.1620009114

Zusammenfassung

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 can mediate 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.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

ABC transporter, conformational dynamics, membrane proteins, peptide transport, transporter associated with antigen processing

Zitieren

ISO 690

NÖLL, Anne, Christoph THOMAS, Valentina HERBRING, Tina ZOLLMANN, Katja BARTH, Ahmad Reza MEHDIPOUR, Thomas M. TOMASIAK, Kay DIEDERICHS, Robert M. STROUD, Robert TAMPÉ, 2017. Crystal structure and mechanistic basis of a functional homolog of the antigen transporter TAP. In: Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2017, 114(4), pp. E438-E447. ISSN 0027-8424. eISSN 1091-6490. Available under: doi: 10.1073/pnas.1620009114

BibTex

@article{Noll2017-01-24Cryst-38128,
  year={2017},
  doi={10.1073/pnas.1620009114},
  title={Crystal structure and mechanistic basis of a functional homolog of the antigen transporter TAP},
  number={4},
  volume={114},
  issn={0027-8424},
  journal={Proceedings of the National Academy of Sciences of the United States of America (PNAS)},
  pages={E438--E447},
  author={Nöll, Anne and Thomas, Christoph and Herbring, Valentina and Zollmann, Tina and Barth, Katja and Mehdipour, Ahmad Reza and Tomasiak, Thomas M. and Diederichs, Kay and Stroud, Robert M. and Tampé, Robert}
}

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Universitätsbibliographie

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