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

作者：Blees Andreas; Reichel Katrin; Trowitzsch Simon; Fisette Olivier; Bock Christoph; Abele Rupert; Hummer Gerhard; Schaefer Lars V; Tampe Robert

来源：Scientific Reports, 2015, 5(1): 17341.

DOI：10.1038/srep17341

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.

• 出版日期2015-11-27