{"doi":"10.1016/j.str.2021.01.003","title":"Interplay between hevin, SPARC, and MDGAs: Modulators of neurexin-neuroligin transsynaptic bridges","abstract":null,"journal":"Structure","year":2021,"id":684293,"datarank":0.5495342469194471,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.0,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":468280,"name":"Shanti Pal Gangwar","orcid":"0000-0003-1024-7608","position":1,"is_corresponding":false},{"id":30205,"name":"Mischa Machius","orcid":"0000-0002-6040-1362","position":2,"is_corresponding":false},{"id":916065,"name":"Gabby Rudenko","orcid":null,"position":3,"is_corresponding":false},{"id":915525,"name":"Shanghua Fan","orcid":"0000-0002-6596-8472","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Interplay between hevin, SPARC, and MDGAs: Modulators of neurexin-neuroligin transsynaptic bridges","abstract":"Hevin is secreted by astrocytes and its synaptogenic effects are antagonized by the related protein, SPARC. Hevin stabilizes neurexin-neuroligin transsynaptic bridges in vivo. A third protein, membrane-tethered MDGA, blocks these bridges. Here, we reveal the molecular underpinnings of a regulatory network formed by this trio of proteins. The hevin FS-EC structure differs from SPARC, in that the EC domain appears rearranged around a conserved core. The FS domain is structurally conserved and it houses nanomolar affinity binding sites for neurexin and neuroligin. SPARC also binds neurexin and neuroligin, competing with hevin, so its antagonist action is rooted in its shortened N-terminal region. Strikingly, the hevin FS domain competes with MDGA for an overlapping binding site on neuroligin, while the hevin EC domain binds the extracellular matrix protein collagen (like SPARC), so that this trio of proteins can regulate neurexin-neuroligin transsynaptic bridges and also extracellular matrix interactions, impacting synapse formation and ultimately neural circuits.","is_dataset_classified":null,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33535026","pmcid":"PMC8254758","openalex_id":"https://openalex.org/W3126269643","authors":[],"funders":[{"funder_name":"NIMH NIH HHS","grant_id":"R01 MH077303","title":null},{"funder_name":"National Institute of Mental Health","grant_id":"","title":null},{"funder_name":"University of Texas Medical Branch at Galveston","grant_id":"","title":null}],"total_grants":3,"fwci":4.0134,"citation_percentile":0.94656619,"influential_citations":0,"citation_trend":[{"year":2021,"count":3},{"year":2022,"count":10},{"year":2023,"count":5},{"year":2024,"count":8},{"year":2025,"count":9},{"year":2026,"count":3}],"oa_status":"bronze","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"http://www.cell.com/article/S0969212621000034/pdf","host_type":"journal"},{"url":"http://www.cell.com/article/S0969212621000034/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0969212621000034?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0969212621000034?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.str.2021.01.003","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33535026","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8254758","host_type":"repository"}],"fields_of_study":["Bone and Dental Protein Studies","Neurological diseases and metabolism","Amino Acid Enzymes and Metabolism"],"mesh_terms":["Protein Domains","Binding Sites","Calcium-Binding Proteins","Humans","Models, Molecular","Nerve Tissue Proteins","Protein Binding","Protein Conformation","Osteonectin","Extracellular Matrix Proteins","Crystallography, X-Ray","Neural Cell Adhesion Molecules","Protein Interaction Maps"],"keywords":["Neurexin","Neuroligin","Extracellular matrix","Extracellular","Cell biology","Matricellular protein","Biology","Chemistry","Biochemistry","Receptor","Excitatory postsynaptic potential","Adhesion molecule","protein structure","Sparc","Neuropsychiatric Disease","Neurexins","Hevin","Neuroligins","Synaptic Organizer","Mdgas"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"},{"name":"refseq"},{"name":"uniprot"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T13:44:31.709890Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}