{"doi":"10.1101/2022.03.06.483190","title":"Molecular mechanism for strengthening E-cadherin adhesion using a monoclonal antibody","abstract":"Abstract E-cadherin (Ecad) is an essential cell-cell adhesion protein with tumor suppression properties. The adhesive state of Ecad can be modified by the monoclonal antibody 19A11, which has potential applications in reducing cancer metastasis. Using x-ray crystallography, we determine the structure of 19A11 Fab bound to Ecad and show that the antibody binds to the first extracellular domain of Ecad near its primary adhesive motif - the strand-swap dimer interface. Molecular dynamics simulations and single molecule atomic force microscopy demonstrate that 19A11 interacts with Ecad in two distinct modes, one that strengthens the strand-swap dimer and one that does not alter adhesion. We show that adhesion is strengthened by the formation of a salt bridge between 19A11 and Ecad, which in turn stabilizes the swapped β-strand and its complimentary binding pocket. Our results identify mechanistic principles for engineering antibodies to enhance Ecad adhesion.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303008,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":321586,"name":"Allison Maker","orcid":"0000-0002-0622-9872","position":1,"is_corresponding":false},{"id":561161,"name":"Andrew Vae Priest","orcid":null,"position":2,"is_corresponding":false},{"id":317765,"name":"David M. Dranow","orcid":"0000-0003-1871-2455","position":3,"is_corresponding":false},{"id":896503,"name":"Jenny N. Phan","orcid":null,"position":4,"is_corresponding":false},{"id":544309,"name":"Thomas E. Edwards","orcid":"0000-0002-0474-8003","position":5,"is_corresponding":false},{"id":530550,"name":"Bart L. Staker","orcid":"0000-0001-9570-5086","position":6,"is_corresponding":false},{"id":411893,"name":"Peter J. Myler","orcid":"0000-0002-0056-0513","position":7,"is_corresponding":false},{"id":227936,"name":"Barry M. Gumbiner","orcid":"0000-0003-1850-3506","position":8,"is_corresponding":false},{"id":355155,"name":"Sanjeevi Sivasankar","orcid":"0000-0003-2593-0477","position":9,"is_corresponding":false},{"id":574474,"name":"Bin Xie","orcid":"0000-0002-2305-7865","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:20.348385Z","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":[]}