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

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Reichel,  Katrin
Lehrstuhl für Theoretische Chemie, Ruhr-University Bochum, D-44780 Bochum, Germany;
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;

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Hummer,  Gerhard
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;

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Citation

Blees, A., Reichel, K., Trowitzsch, S., Fisette, O., Bock, C., Abele, R., et al. (2015). Assembly of the MHC I peptideloading complex determined by a conserved ionic lock-switch. Scientific Reports, 5: 17341. doi:10.1038/srep17341 1.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002A-47EE-F
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.