{"EMPIAR-10637":{"imagesets":[{"segmentations":[],"name":"Unaligned multi-frame micrographs of the ternary Netrin 1-Neogenin 1-Repulsive Guidance Molecule B complex","directory":"data","category":"micrographs - multiframe","header_format":"TIFF","data_format":"TIFF","num_images_or_tilt_series":1635,"frames_per_image":40,"frame_range_min":null,"frame_range_max":null,"voxel_type":"SIGNED 16 BIT INTEGER","pixel_width":0.85,"pixel_height":0.85,"micrographs_file_pattern":"","picked_particles_file_pattern":"","picked_particles_directory":"","details":"","image_width":"4096","image_height":"4096"}],"workflow_file":null,"grant_references":[],"version_history":[],"title":"Cryo-EM structure of the ternary Netrin 1-Neogenin 1-Repulsive Guidance Molecule B complex","principal_investigator":[{"author_orcid":"0000-0002-6635-3621","middle_name":null,"organization":"Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford","street":"Roosevelt Drive","town_or_city":"Oxford","state_or_province":"Oxfordshire","post_or_zip":"OX3 7BN","telephone":null,"fax":null,"first_name":"Christian","last_name":"Siebold","email":"christian [at] strubi.ox.ac.uk","country":"United Kingdom","entry":"EMPIAR-10637"}],"status":"REL","deposition_date":"2021-02-02","release_date":"2021-04-06","obsolete_date":null,"update_date":"2022-02-07","corresponding_author":{"author":{"author_orcid":"0000-0002-4847-5529","middle_name":null,"organization":"Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford","street":"Roosevelt Drive","town_or_city":"Oxford","state_or_province":"Oxfordshire","post_or_zip":"OX3 7BN","first_name":"Tomas","last_name":"Malinauskas","country":"United Kingdom"}},"authors":[{"author":{"name":"Robinson RA","author_orcid":"0000-0002-1482-0910"}},{"author":{"name":"Griffiths SC","author_orcid":"0000-0002-9257-7354"}},{"author":{"name":"van de Haar LL","author_orcid":"0000-0003-3800-7999"}},{"author":{"name":"Malinauskas T","author_orcid":"0000-0002-4847-5529"}},{"author":{"name":"van Battum EY","author_orcid":"0000-0002-3358-5039"}},{"author":{"name":"Zelina P","author_orcid":null}},{"author":{"name":"Schwab RA","author_orcid":null}},{"author":{"name":"Karia D","author_orcid":"0000-0002-3776-1650"}},{"author":{"name":"Malinauskaite L","author_orcid":"0000-0003-3232-0415"}},{"author":{"name":"Brignani S","author_orcid":"0000-0002-4732-9984"}},{"author":{"name":"van den Munkhof M","author_orcid":"0000-0003-2886-4380"}},{"author":{"name":"Dudukcu O","author_orcid":null}},{"author":{"name":"De Ruiter AA","author_orcid":null}},{"author":{"name":"Van den Heuvel DMA","author_orcid":null}},{"author":{"name":"Bishop B","author_orcid":"0000-0002-1854-7480"}},{"author":{"name":"Elegheert J","author_orcid":"0000-0002-4196-4813"}},{"author":{"name":"Aricescu AR","author_orcid":"0000-0003-3783-1388"}},{"author":{"name":"Pasterkamp RJ","author_orcid":"0000-0003-1631-6440"}},{"author":{"name":"Siebold C","author_orcid":"0000-0002-6635-3621"}}],"cross_references":["EMD-12286"],"biostudies_references":[],"idr_references":[],"empiar_references":[],"citation":[{"authors":[{"name":"Robinson RA","author_orcid":"0000-0002-1482-0910"},{"name":"Griffiths SC","author_orcid":"0000-0002-9257-7354"},{"name":"van de Haar LL","author_orcid":"0000-0003-3800-7999"},{"name":"Malinauskas T","author_orcid":"0000-0002-4847-5529"},{"name":"van Battum EY","author_orcid":"0000-0002-3358-5039"},{"name":"Zelina P","author_orcid":null},{"name":"Schwab RA","author_orcid":null},{"name":"Karia D","author_orcid":"0000-0002-3776-1650"},{"name":"Malinauskaite L","author_orcid":"0000-0003-3232-0415"},{"name":"Brignani S","author_orcid":"0000-0002-4732-9984"},{"name":"van den Munkhof M","author_orcid":"0000-0003-2886-4380"},{"name":"Dudukcu O","author_orcid":null},{"name":"De Ruiter AA","author_orcid":null},{"name":"Van den Heuvel DMA","author_orcid":null},{"name":"Bishop B","author_orcid":"0000-0002-1854-7480"},{"name":"Elegheert J","author_orcid":"0000-0002-4196-4813"},{"name":"Aricescu AR","author_orcid":"0000-0003-3783-1388"},{"name":"Pasterkamp RJ","author_orcid":"0000-0003-1631-6440"},{"name":"Siebold C","author_orcid":"0000-0002-6635-3621"}],"editors":[],"published":true,"j_or_nj_citation":true,"title":"Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling","volume":null,"country":"","first_page":null,"last_page":null,"year":"2021","language":"English","doi":"10.1016/j.cell.2021.02.045","pubmedid":"33740419","details":"During cell migration or differentiation, cell surface receptors are exposed to different ligands. However, how the signals from simultaneously presented extracellular ligands are integrated remains incompletely understood. Neogenin (NEO1) acts as an attractive guidance receptor upon Netrin-1 (NET1) binding but mediates repulsion via Repulsive Guidance Molecules (RGMs). Here, we identify a mechanism of signal integration through the formation of a ternary NEO1-NET1-RGM complex triggering reciprocal silencing of downstream signaling. We determine structures of the NEO1-NET1-RGM complex, revealing a defined ‘trimer-of-trimers’ super-assembly, and demonstrate that this complex can exist in the cell membrane. Formation of this super-assembly results in inhibition of RGMA-NEO1-mediated growth cone collapse and RGMA- or NET1-NEO1-mediated neuron migration, by preventing signalling-compatible RGM-NEO1 complexes and NET1-induced NEO1 ectodomain clustering. These results illustrate how simultaneous binding of ligands with opposing functions to a single receptor does not lead to competition for binding, but to formation of a super-complex that diminishes their functional outputs.","book_chapter_title":null,"publisher":null,"publication_location":null,"journal":"Cell","journal_abbreviation":"Cell","issue":null,"preprint":false}],"dataset_size":"1.2 TB","experiment_type":"EMDB","scale":null,"related_pdb_entries":["7ndg"],"entry_doi":"10.6019/EMPIAR-10637"}}