Dataset Information

Dissociation of β2m from MHC Class I triggers formation of noncovalent, transient heavy chain dimers

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 (beta2m), 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 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 the beta2m light chain.

INSTRUMENT(S): Q-Tof ultima

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Janine-Denise Kopicki

LAB HEAD: Charlotte Uetrecht

PROVIDER: PXD033485 | Pride | 2022-05-11

REPOSITORIES: Pride

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

Dirscherl Cindy C Löchte Sara S Hein Zeynep Z Kopicki Janine-Denise JD Harders Antonia Regina AR Linden Noemi N Karner Andreas A Preiner Johannes J Weghuber Julian J Garcia-Alai Maria M Uetrecht Charlotte C Zacharias Martin M Piehler Jacob J Lanzerstorfer Peter P Springer Sebastian S

Journal of cell science 20220513 9

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 (β2m, 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 photo ...[more]

PMID: 35393611

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Dataset Information

Dissociation of β2m from MHC Class I triggers formation of noncovalent, transient heavy chain dimers

Publications

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

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