TAPBPR mediates peptide dissociation from MHC class I using a leucine lever.
dc.contributor.author | Ilca, F Tudor | |
dc.contributor.author | Neerincx, Andreas | |
dc.contributor.author | Hermann, Clemens | |
dc.contributor.author | Marcu, Ana | |
dc.contributor.author | Stevanović, Stefan | |
dc.contributor.author | Deane, Janet E | |
dc.contributor.author | Boyle, Louise H | |
dc.date.accessioned | 2018-12-20T00:30:36Z | |
dc.date.available | 2018-12-20T00:30:36Z | |
dc.date.issued | 2018-11-28 | |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/287215 | |
dc.description.abstract | Tapasin and TAPBPR are known to perform peptide editing on major histocompatibility complex class I (MHC I) molecules; however, the precise molecular mechanism(s) involved in this process remain largely enigmatic. Here, using immunopeptidomics in combination with novel cell-based assays that assess TAPBPR-mediated peptide exchange, we reveal a critical role for the K22-D35 loop of TAPBPR in mediating peptide exchange on MHC I. We identify a specific leucine within this loop that enables TAPBPR to facilitate peptide dissociation from MHC I. Moreover, we delineate the molecular features of the MHC I F pocket required for TAPBPR to promote peptide dissociation in a loop-dependent manner. These data reveal that chaperone-mediated peptide editing on MHC I can occur by different mechanisms dependent on the C-terminal residue that the MHC I accommodates in its F pocket and provide novel insights that may inform the therapeutic potential of TAPBPR manipulation to increase tumour immunogenicity. | |
dc.description.sponsorship | Wellcome PhD studentship (109076/Z/15/A). Wellcome Senior Research Fellowship (104647/Z/14/Z) South African Medical Research Council Bosch-Forschungsstiftung. Royal Society University Research Fellowship (UF100371). | |
dc.format.medium | Electronic | |
dc.language | eng | |
dc.publisher | eLife Sciences Publications, Ltd | |
dc.subject | Hela Cells | |
dc.subject | Humans | |
dc.subject | Leucine | |
dc.subject | Peptides | |
dc.subject | Immunoglobulins | |
dc.subject | Membrane Proteins | |
dc.subject | Histocompatibility Antigens Class I | |
dc.subject | HLA-A Antigens | |
dc.subject | Antigen Presentation | |
dc.subject | Binding Sites | |
dc.subject | Amino Acid Sequence | |
dc.subject | Protein Binding | |
dc.subject | Mutation | |
dc.subject | Molecular Docking Simulation | |
dc.subject | Protein Domains | |
dc.title | TAPBPR mediates peptide dissociation from MHC class I using a leucine lever. | |
dc.type | Article | |
prism.publicationDate | 2018 | |
prism.publicationName | Elife | |
prism.volume | 7 | |
dc.identifier.doi | 10.17863/CAM.34522 | |
dcterms.dateAccepted | 2018-11-28 | |
rioxxterms.versionofrecord | 10.7554/eLife.40126 | |
rioxxterms.version | AM | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2018-11-28 | |
dc.contributor.orcid | Ilca, F Tudor [0000-0002-6582-8007] | |
dc.contributor.orcid | Neerincx, Andreas [0000-0002-6902-5383] | |
dc.contributor.orcid | Hermann, Clemens [0000-0002-0009-9501] | |
dc.contributor.orcid | Marcu, Ana [0000-0003-0808-8097] | |
dc.contributor.orcid | Stevanović, Stefan [0000-0003-1954-7762] | |
dc.contributor.orcid | Deane, Janet E [0000-0002-4863-0330] | |
dc.contributor.orcid | Boyle, Louise H [0000-0002-3105-6555] | |
dc.identifier.eissn | 2050-084X | |
rioxxterms.type | Journal Article/Review | |
pubs.funder-project-id | Wellcome Trust (104647/Z/14/Z) | |
pubs.funder-project-id | Royal Society (UF150682) | |
pubs.funder-project-id | Wellcome Trust (109076/Z/15/Z) | |
cam.issuedOnline | 2018-11-28 | |
rioxxterms.freetoread.startdate | 2019-11-28 |
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