Dissociation of β2m from MHC class I triggers formation of noncovalent transient heavy chain dimers: Dissociation of β2m from MHC class I triggers formation of noncovalent transient heavy chain dimers

Cindy Dirscherl, Sara Löchte, Zeynep Hein, Janine-Denise Kopicki, Antonia Regina Harders, Noemi Linden, Andreas Karner, Johannes Preiner, Julian Weghuber, Maria Garcia-Alai, Charlotte Uetrecht, Martin Zacharias, Jacob Piehler, Peter Lanzerstorfer, Sebastian Springer

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

5 Zitate (Scopus)

Abstract

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 (β 2m, 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 micropattern 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 α 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 α 3 domain of one FHC binds to another FHC in a manner similar to that seen for β 2m.

OriginalspracheEnglisch
Aufsatznummerjcs259498
FachzeitschriftJournal of Cell Science
Jahrgang135
Ausgabenummer9
DOIs
PublikationsstatusVeröffentlicht - Mai 2022

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