{"doi":"10.1016/j.celrep.2021.109834","title":"ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes","abstract":"WNTs play key roles in development and disease, signaling through Frizzled (FZD) seven-pass transmembrane receptors and numerous co-receptors including ROR and RYK family receptor tyrosine kinases (RTKs). We describe crystal structures and WNT-binding characteristics of extracellular regions from the Drosophila ROR and RYK orthologs Nrk (neurospecific receptor tyrosine kinase) and Derailed-2 (Drl-2), which bind WNTs though a FZD-related cysteine-rich domain (CRD) and WNT-inhibitory factor (WIF) domain respectively. Our crystal structures suggest that neither Nrk nor Drl-2 can accommodate the acyl chain typically attached to WNTs. The Nrk CRD contains a deeply buried bound fatty acid, unlikely to be exchangeable. The Drl-2 WIF domain lacks the lipid-binding site seen in WIF-1. We also find that recombinant DWnt-5 can bind Drosophila ROR and RYK orthologs despite lacking an acyl chain. Alongside analyses of WNT/receptor interaction sites, our structures provide further insight into how WNTs may recruit RTK co-receptors into signaling complexes.","journal":"Cell Reports","year":2021,"id":171176,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9619,"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":705747,"name":"Jeannine M. Mendrola","orcid":null,"position":1,"is_corresponding":false},{"id":279238,"name":"Joshua B. Sheetz","orcid":"0000-0003-2052-1252","position":2,"is_corresponding":false},{"id":705091,"name":"Neo Wu","orcid":"0000-0003-2389-9584","position":3,"is_corresponding":false},{"id":705092,"name":"Anselm Sommer","orcid":"0000-0002-6485-4860","position":4,"is_corresponding":false},{"id":705093,"name":"Kelsey F. Speer","orcid":"0000-0002-9828-1888","position":5,"is_corresponding":false},{"id":705748,"name":"Jasprina N. Noordermeer","orcid":null,"position":6,"is_corresponding":false},{"id":705094,"name":"Zhong-Yuan Kan","orcid":"0000-0001-6689-0593","position":7,"is_corresponding":false},{"id":373858,"name":"Kay Perry","orcid":"0000-0002-4046-1704","position":8,"is_corresponding":false},{"id":364139,"name":"S. Walter Englander","orcid":"0000-0002-4802-2175","position":9,"is_corresponding":false},{"id":279245,"name":"Steven E. Stayrook","orcid":"0000-0002-1677-8293","position":10,"is_corresponding":false},{"id":387549,"name":"Lee G. Fradkin","orcid":"0000-0002-5282-2984","position":11,"is_corresponding":false},{"id":279249,"name":"Mark A. Lemmon","orcid":"0000-0002-3379-5319","position":12,"is_corresponding":false},{"id":705746,"name":"Fumin Shi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":100,"raw_metadata":null,"created_at":"2026-07-18T23:46:28.747384Z","pmid":"34686333","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":[]}