Dissociation of beta(2)m from MHC class I triggers formation of noncovalent transient heavy chain dimers
Autor(en): | Dirscherl, Cindy Loechte, Sara Hein, Zeynep Kopicki, Janine-Denise Harders, Antonia Regina Linden, Noemi Karner, Andreas Preiner, Johannes Weghuber, Julian Garcia-Alai, Maria Uetrecht, Charlotte Zacharias, Martin Piehler, Jacob Lanzerstorfer, Peter Springer, Sebastian |
Stichwörter: | Antigen presentation; ASSOCIATION; Cell Biology; DIMERIZATION; HLA CLASS-I; Major histocompatibility complex class I; MASS; MHC-I; MOBILITY; MOLECULES; OPEN CONFORMERS; Protein oligomerization; PROTEINS; RECEPTOR; SURFACE | Erscheinungsdatum: | 2022 | Herausgeber: | COMPANY BIOLOGISTS LTD | Journal: | JOURNAL OF CELL SCIENCE | Volumen: | 135 | Ausgabe: | 9 | Zusammenfassung: | At the plasma membrane of mammalian cells, major histocompatibility complex class I molecules (MHC-I) present antigenic peptides to cytotoxic T cells. Following the loss of the peptide and the light chain beta-2 microglobulin ((beta(2)m, encoded by B2M), the resulting free heavy chains (FHCs) can associate into homotypic complexes in the plasma membrane. Here, we investigate the stoichiometry and dynamics of MHC-I FHCs assemblies by combining a micropattem assay with fluorescence recovery after photobleaching (FRAP) and with single-molecule co-tracking. We identify non-covalent MHC-I FHC dimers, with dimerization mediated by the alpha(3) domain, as the prevalent species at the plasma membrane, leading a moderate decrease in the diffusion coefficient. MHC-I FHC dimers show increased tendency to cluster into higher order oligomers as concluded from an increased immobile fraction with higher single-molecule colocalization. In vitro studies with isolated proteins in conjunction with molecular docking and dynamics simulations suggest that in the complexes, the alpha(3) domain of one FHC binds to another FHC in a manner similar to that seen for beta(2)m. |
ISSN: | 0021-9533 | DOI: | 10.1242/jcs.259498 |
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geprüft am 09.05.2024