Molecular basis for Jagged-1/Serrate ligand recognition by the Notch receptor.
dc.contributor.author | Whiteman, P | en |
dc.contributor.author | de Madrid, BH | en |
dc.contributor.author | Taylor, P | en |
dc.contributor.author | Li, D | en |
dc.contributor.author | Heslop, R | en |
dc.contributor.author | Viticheep, N | en |
dc.contributor.author | Tan, JZ | en |
dc.contributor.author | Shimizu, H | en |
dc.contributor.author | Callaghan, J | en |
dc.contributor.author | Masiero, M | en |
dc.contributor.author | Li, JL | en |
dc.contributor.author | Banham, AH | en |
dc.contributor.author | Harris, AL | en |
dc.contributor.author | Lea, SM | en |
dc.contributor.author | Redfield, C | en |
dc.contributor.author | Baron, M | en |
dc.contributor.author | Handford, PA | en |
dc.date.accessioned | 2017-11-27T19:58:48Z | |
dc.date.available | 2017-11-27T19:58:48Z | |
dc.date.issued | 2013-03-08 | en |
dc.identifier.uri | http://hdl.handle.net/10026.1/10337 | |
dc.description.abstract |
We have mapped a Jagged/Serrate-binding site to specific residues within the 12th EGF domain of human and Drosophila Notch. Two critical residues, involved in a hydrophobic interaction, provide a ligand-binding platform and are adjacent to a Fringe-sensitive residue that modulates Notch activity. Our data suggest that small variations within the binding site fine-tune ligand specificity, which may explain the observed sequence heterogeneity in mammalian Notch paralogues, and should allow the development of paralogue-specific ligand-blocking antibodies. As a proof of principle, we have generated a Notch-1-specific monoclonal antibody that blocks binding, thus paving the way for antibody tools for research and therapeutic applications. | en |
dc.format.extent | 7305 - 7312 | en |
dc.language | eng | en |
dc.language.iso | eng | en |
dc.subject | Amino Acid Sequence | en |
dc.subject | Animals | en |
dc.subject | Antibodies, Monoclonal | en |
dc.subject | Blotting, Western | en |
dc.subject | Calcium-Binding Proteins | en |
dc.subject | Cell Line | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Drosophila Proteins | en |
dc.subject | Flow Cytometry | en |
dc.subject | HEK293 Cells | en |
dc.subject | Humans | en |
dc.subject | Intercellular Signaling Peptides and Proteins | en |
dc.subject | Jagged-1 Protein | en |
dc.subject | Ligands | en |
dc.subject | Membrane Proteins | en |
dc.subject | Mice | en |
dc.subject | Models, Molecular | en |
dc.subject | Molecular Sequence Data | en |
dc.subject | Mutation | en |
dc.subject | Protein Binding | en |
dc.subject | Protein Structure, Secondary | en |
dc.subject | Protein Structure, Tertiary | en |
dc.subject | Receptor, Notch1 | en |
dc.subject | Receptors, Notch | en |
dc.subject | Sequence Homology, Amino Acid | en |
dc.subject | Serrate-Jagged Proteins | en |
dc.title | Molecular basis for Jagged-1/Serrate ligand recognition by the Notch receptor. | en |
dc.type | Journal Article | |
plymouth.author-url | https://www.ncbi.nlm.nih.gov/pubmed/23339193 | en |
plymouth.issue | 10 | en |
plymouth.volume | 288 | en |
plymouth.publication-status | Published | en |
plymouth.journal | J Biol Chem | en |
dc.identifier.doi | 10.1074/jbc.M112.428854 | en |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine/UoA01 Clinical Medicine | |
dc.publisher.place | United States | en |
dc.identifier.eissn | 1083-351X | en |
dc.rights.embargoperiod | Not known | en |
rioxxterms.versionofrecord | 10.1074/jbc.M112.428854 | en |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | en |
rioxxterms.type | Journal Article/Review | en |