dc.contributor.author | Kliche, J | |
dc.contributor.author | Garvanska, DH | |
dc.contributor.author | Simonetti, L | |
dc.contributor.author | Badgujar, D | |
dc.contributor.author | Dobritzsch, D | |
dc.contributor.author | Nilsson, J | |
dc.contributor.author | Davey, NE | |
dc.contributor.author | Ivarsson, Y | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2023-08-15T14:03:53Z | |
dc.date.available | 2023-08-15T14:03:53Z | |
dc.date.issued | 2023-07-11 | |
dc.identifier | ARTN e11164 | |
dc.identifier.citation | Molecular Systems Biology, 2023, 19 (7), pp. e11164 - | en_US |
dc.identifier.issn | 1744-4292 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5935 | |
dc.identifier.eissn | 1744-4292 | |
dc.identifier.eissn | 1744-4292 | |
dc.identifier.doi | 10.15252/msb.202211164 | |
dc.description.abstract | Phosphorylation is a ubiquitous post-translation modification that regulates protein function by promoting, inhibiting or modulating protein-protein interactions. Hundreds of thousands of phosphosites have been identified but the vast majority have not been functionally characterised and it remains a challenge to decipher phosphorylation events modulating interactions. We generated a phosphomimetic proteomic peptide-phage display library to screen for phosphosites that modulate short linear motif-based interactions. The peptidome covers ~13,500 phospho-serine/threonine sites found in the intrinsically disordered regions of the human proteome. Each phosphosite is represented as wild-type and phosphomimetic variant. We screened 71 protein domains to identify 248 phosphosites that modulate motif-mediated interactions. Affinity measurements confirmed the phospho-modulation of 14 out of 18 tested interactions. We performed a detailed follow-up on a phospho-dependent interaction between clathrin and the mitotic spindle protein hepatoma-upregulated protein (HURP), demonstrating the essentiality of the phospho-dependency to the mitotic function of HURP. Structural characterisation of the clathrin-HURP complex elucidated the molecular basis for the phospho-dependency. Our work showcases the power of phosphomimetic ProP-PD to discover novel phospho-modulated interactions required for cellular function. | |
dc.format | Print-Electronic | |
dc.format.extent | e11164 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | WILEY | en_US |
dc.relation.ispartof | Molecular Systems Biology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | clathrin | |
dc.subject | phage display | |
dc.subject | phosphomimetic mutation | |
dc.subject | phosphorylation | |
dc.subject | protein-protein interactions | |
dc.subject | Humans | |
dc.subject | Proteomics | |
dc.subject | Peptide Library | |
dc.subject | Phosphorylation | |
dc.subject | Clathrin | |
dc.title | Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-05-03 | |
dc.date.updated | 2023-08-15T14:02:59Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.15252/msb.202211164 | en_US |
rioxxterms.licenseref.startdate | 2023-07-11 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37219487 | |
pubs.issue | 7 | |
pubs.organisational-group | /ICR | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.15252/msb.202211164 | |
pubs.volume | 19 | |
icr.researchteam | Short Linear Motif | en_US |
dc.contributor.icrauthor | Davey, Norman | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Robert Huddart) on 2023-08-15. Deposit type is initial. No. of files: 1. Files: Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions.pdf | |