{"doi":"10.1038/s41467-021-24367-3","title":"Structural basis of the activation of c-MET receptor","abstract":"The c-MET receptor is a receptor tyrosine kinase (RTK) that plays essential roles in normal cell development and motility. Aberrant activation of c-MET can lead to both tumors growth and metastatic progression of cancer cells. C-MET can be activated by either hepatocyte growth factor (HGF), or its natural isoform NK1. Here, we report the cryo-EM structures of c-MET/HGF and c-MET/NK1 complexes in the active state. The c-MET/HGF complex structure reveals that, by utilizing two distinct interfaces, one HGF molecule is sufficient to induce a specific dimerization mode of c-MET for receptor activation. The binding of heparin as well as a second HGF to the 2:1 c-MET:HGF complex further stabilize this active conformation. Distinct to HGF, NK1 forms a stable dimer, and bridges two c-METs in a symmetrical manner for activation. Collectively, our studies provide structural insights into the activation mechanisms of c-MET, and reveal how two isoforms of the same ligand use dramatically different mechanisms to activate the receptor.","journal":"Nature Communications","year":2021,"id":147904,"datarank":0.7465100613630863,"base_score":4.976733742420574,"endowment":4.976733742420574,"self_citation_contribution":0.7465100613630863,"citation_network_contribution":0.0,"self_endowment_contribution":0.7465100613630863,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":144,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":340460,"name":"Zhiming Chen","orcid":"0000-0002-2423-101X","position":1,"is_corresponding":false},{"id":406591,"name":"Guan-Yu Xiao","orcid":"0000-0003-3454-6717","position":2,"is_corresponding":false},{"id":108352,"name":"Xuewu Zhang","orcid":"0000-0002-3634-6711","position":3,"is_corresponding":false},{"id":108353,"name":"Xiao‐chen Bai","orcid":"0000-0002-4234-5686","position":4,"is_corresponding":false},{"id":412242,"name":"Emiko Uchikawa","orcid":"0000-0003-0442-767X","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:42:35.448762Z","pmid":"34210960","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":[]}