Light control of the peptide-loading complex synchronizes antigen translocation and MHC I trafficking

  • Antigen presentation via major histocompatibility complex class I (MHC I) molecules is essential to mount an adaptive immune response against pathogens and cancerous cells. To this end, the transporter associated with antigen processing (TAP) delivers snippets of the cellular proteome, resulting from proteasomal degradation, into the ER lumen. After peptide loading and editing by the peptide-loading complex (PLC), stable peptide-MHC I complexes are released for cell surface presentation. Since the process of MHC I trafficking is poorly defined, we established an approach to control antigen presentation by introduction of a photo-caged amino acid in the catalytic ATP-binding site of TAP. By optical control, we initiate TAP-dependent antigen translocation, thus providing new insights into TAP function within the PLC and MHC I trafficking in living cells. Moreover, this versatile approach has the potential to be applied in the study of other cellular pathways controlled by P-loop ATP/GTPases.
Author:Jamina Brunnberg, Valentina HerbringGND, Esteban Günther CastilloORCiD, Heike KrügerGND, Ralph WienekeORCiDGND, Robert TampéORCiDGND
Parent Title (English):Communications biology
Publisher:Springer Nature
Place of publication:London
Document Type:Article
Date of Publication (online):2021/03/30
Date of first Publication:2021/03/30
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/10/13
Tag:Chemical modification; Membranes; Transporters
Issue:art. 430
Article Number:430
Page Number:10
First Page:1
Last Page:10
The work was supported by the German Research Foundation (GRK 1986 to R.W. and R.T.; TA 157/12-1 and CRC 807—Membrane Transport and Communication to R.T.), as well as by the European Research Council (ERC Advanced Grant 789121 to R.T.). Open Access funding enabled and organized by Projekt DEAL.
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International