PXD033485

PXD033485 is an original dataset announced via ProteomeXchange.

Title	Dissociation of β2m from MHC Class I triggers formation of noncovalent, transient heavy chain dimers
Description	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.
HostingRepository	PRIDE
AnnounceDate	2022-05-11
AnnouncementXML	Submission_2022-05-11_07:39:06.719.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Janine-Denise Kopicki
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q-Tof Ultima

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-28 00:24:42	ID requested
⏵ 1	2022-05-11 07:39:07	announced

10.1242/JCS.259498;

Dirscherl C, L, ö, chte S, Hein Z, Kopicki JD, Harders AR, Linden N, Karner A, Preiner J, Weghuber J, Garcia-Alai M, Uetrecht C, Zacharias M, Piehler J, Lanzerstorfer P, Springer S, 2m from MHC class I triggers formation of noncovalent transient heavy chain dimers. J Cell Sci, 135(9):(2022) [pubmed]

submitter keyword: human, MHC class I, HLA-A, dimerization, native MS

Charlotte Uetrecht
contact affiliation	Leibniz Institute for Virology (LIV), Germany; Centre for Structural Systems Biology (CSSB), Germany; University of Siegen, Germany; Deutsches Elektronen-Synchrotron (DESY), Germany; European XFEL GmbH, Germany.
contact email	charlotte.uetrecht@cssb-hamburg.de
lab head
Janine-Denise Kopicki
contact affiliation	CSSB Centre for Structural Systems Biology
contact email	janine.kopicki@leibniz-hpi.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033485
     1. Label: PRIDE project
     2. Name: Dissociation of β2m from MHC Class I triggers formation of noncovalent, transient heavy chain dimers