1. Academic Validation
  2. Assembly of the MHC I peptide-loading complex determined by a conserved ionic lock-switch

Assembly of the MHC I peptide-loading complex determined by a conserved ionic lock-switch

  • Sci Rep. 2015 Nov 27;5:17341. doi: 10.1038/srep17341.
Andreas Blees 1 Katrin Reichel 2 3 Simon Trowitzsch 1 Olivier Fisette 2 Christoph Bock 1 Rupert Abele 1 Gerhard Hummer 3 Lars V Schäfer 2 Robert Tampé 1 4
Affiliations

Affiliations

  • 1 Institute of Biochemistry, Biocenter, Goethe-University Frankfurt am Main, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.
  • 2 Lehrstuhl für Theoretische Chemie, Ruhr-University Bochum, D-44780 Bochum, Germany.
  • 3 Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, D-60438 Frankfurt am Main, Germany.
  • 4 Cluster of Excellence-Macromolecular Complexes, Goethe-University Frankfurt am Main, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.
Abstract

Salt bridges in lipid bilayers play a decisive role in the dynamic assembly and downstream signaling of the natural killer and T-cell receptors. Here, we describe the identification of an inter-subunit salt bridge in the membrane within yet another key component of the immune system, the peptide-loading complex (PLC). The PLC regulates cell surface presentation of self-antigens and antigenic Peptides via molecules of the major histocompatibility complex class I. We demonstrate that a single salt bridge in the membrane between the transporter associated with antigen processing TAP and the MHC I-specific chaperone tapasin is essential for the assembly of the PLC and for efficient MHC I antigen presentation. Molecular modeling and all-atom molecular dynamics simulations suggest an ionic lock-switch mechanism for the binding of TAP to tapasin, in which an unfavorable uncompensated charge in the ER-membrane is prevented through complex formation. Our findings not only deepen the understanding of the interaction network within the PLC, but also provide evidence for a general interaction principle of dynamic multiprotein membrane complexes in immunity.

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