{"doi":"10.1126/science.adr1752","title":"Structural basis for nucleolin recognition of <i>MYC</i> promoter G-quadruplex","abstract":"The MYC oncogene promoter G-quadruplex (MycG4) regulates transcription and is a prevalent G4 locus in immortal cells. Nucleolin, a major MycG4-binding protein, exhibits greater affinity for MycG4 than for nucleolin recognition element (NRE) RNA. Nucleolin’s four RNA binding domains (RBDs) are essential for high-affinity MycG4 binding. We present the 2.6-angstrom crystal structure of the nucleolin-MycG4 complex, revealing a folded parallel three-tetrad G-quadruplex with two coordinating potassium ions (K + ), interacting with RBD1, RBD2, and Linker12 through its 6–nucleotide (nt) central loop and 5′ flanking region. RBD3 and RBD4 bind MycG4’s 1-nt loops as demonstrated by nuclear magnetic resonance (NMR). Cleavage under targets and tagmentation sequencing confirmed nucleolin’s binding to MycG4 in cells. Our results revealed a G4 conformation-based recognition by a regulating protein through multivalent interactions, suggesting that G4s are nucleolin’s primary cellular substrates, indicating G4 epigenetic transcriptional regulation and helping G4-targeted drug discovery.","journal":"Science","year":2025,"id":509252,"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":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":644245,"name":"Jonathan Dickerhoff","orcid":"0000-0002-3197-9472","position":1,"is_corresponding":false},{"id":1363134,"name":"Ke‐wei Zheng","orcid":"0000-0002-4110-4776","position":2,"is_corresponding":false},{"id":266717,"name":"Satchal K. Erramilli","orcid":"0000-0001-8694-7681","position":3,"is_corresponding":false},{"id":262651,"name":"Hanqiao Feng","orcid":"0000-0003-3488-0600","position":4,"is_corresponding":false},{"id":348792,"name":"Guanhui Wu","orcid":"0000-0003-4659-8717","position":5,"is_corresponding":false},{"id":1363988,"name":"Buket Onel","orcid":null,"position":6,"is_corresponding":false},{"id":1363135,"name":"Yuwei Chen","orcid":"0009-0000-1198-3928","position":7,"is_corresponding":false},{"id":695043,"name":"Kai‐Bo Wang","orcid":"0000-0002-2934-9906","position":8,"is_corresponding":false},{"id":432866,"name":"Megan Carver","orcid":"0000-0003-3637-5253","position":9,"is_corresponding":false},{"id":1363136,"name":"Clement Lin","orcid":"0000-0001-7054-3455","position":10,"is_corresponding":false},{"id":1363137,"name":"Saburo Sakai","orcid":"0000-0002-3809-0254","position":11,"is_corresponding":false},{"id":300846,"name":"Jun Wan","orcid":"0000-0001-9286-6562","position":12,"is_corresponding":false},{"id":1363138,"name":"Charles Vinson","orcid":"0000-0001-7453-1793","position":13,"is_corresponding":false},{"id":315695,"name":"Laurence H. Hurley","orcid":"0000-0002-8522-450X","position":14,"is_corresponding":false},{"id":260362,"name":"Anthony A. Kossiakoff","orcid":"0000-0003-3174-9359","position":15,"is_corresponding":false},{"id":494456,"name":"Nanjie Deng","orcid":"0000-0001-8805-3526","position":16,"is_corresponding":false},{"id":262655,"name":"Yawen Bai","orcid":"0000-0003-3239-1109","position":17,"is_corresponding":false},{"id":352782,"name":"Nicholas Noinaj","orcid":"0000-0001-6361-2336","position":18,"is_corresponding":false},{"id":348794,"name":"Danzhou Yang","orcid":"0000-0001-7489-7111","position":19,"is_corresponding":false},{"id":1363133,"name":"Luying Chen","orcid":"0000-0001-5136-4945","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:47:24.513904Z","pmid":"40245140","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":[]}