TY  - JOUR
A1  - Blees, Andreas
A1  - Reichel, Katrin
A1  - Trowitzsch, Simon
A1  - Fisette, Olivier
A1  - Bock, Christoph
A1  - Abele, Rupert
A1  - Hummer, Gerhard
A1  - Schäfer, Lars
A1  - Tampé, Robert
T1  - Assembly of the MHC 1 peptide-loading complex determined by a conserved ionic lock-switch
T2  - Scientific reports
N2  - 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.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37394
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-373943
SN  - 2045-2322
N1  - 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 http://creativecommons.org/licenses/by/4.0/
VL  - 5
IS  - 17341
SP  - 1
EP  - 11
PB  - Nature Publishing Group
CY  - London
ER  -