Assembly of the MHC 1 peptide-loading complex determined by a conserved ionic lock-switch

  • 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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Author:Andreas Blees, Katrin ReichelGND, Simon TrowitzschORCiDGND, Olivier Fisette, Christoph Bock, Rupert AbeleORCiDGND, Gerhard HummerORCiD, Lars Schäfer, Robert TampéORCiDGND
Pubmed Id:
Parent Title (English):Scientific reports
Publisher:Nature Publishing Group
Place of publication:London
Document Type:Article
Date of Publication (online):2015/11/27
Date of first Publication:2015/11/27
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2016/01/28
Page Number:11
First Page:1
Last Page:11
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0