{"doi":"10.1007/s12104-025-10236-3","title":"NMR 1H, 13C, and 15N resonance assignments of the oncogenic Q61R variant of human NRAS in the active, GTP-bound conformation","abstract":"Abstract NRAS Q61R is a frequent mutation in melanoma. Hydrolysis of GTP by NRAS Q61R is reported to be much slower than other KRAS and NRAS mutants. Recent structural biology efforts for KRAS and NRAS proteins have been limited to X-ray crystallography and therefore lack insight into the structure and dynamics of these proteins in solution. Here we report the 1 H N , 15 N, and 13 C backbone and sidechain resonance assignments of the G-domain of oncogenic NRAS Q61R -GTP (MW 19.3 kDa; aa 1–169) using heteronuclear, multidimensional NMR spectroscopy. NRAS Q61R -GTP is a conformationally stable protein in solution. The 1 H– 15 N correlation cross-peaks in a 2D 1 H– 15 N HSQC spectrum collected after 48 h at 298 K remained intact and only minimal signs of peak-broadening were noted for select residues. High resolution NMR allowed unambiguous assignments of the 1 H– 15 N correlation cross-peaks for all aa residues, except Y40, in addition to a significantly large number of aliphatic and aromatic sidechain resonances. NRAS Q61R -GTP exhibits canonical secondary structural elements in the 5 (five) α-helices, 6 (six) β-strands, and associated loop regions as predicted in TALOS-N and CSI. Order parameter (RCI- S 2 ) values predicted by TALOS-N indicate that the NRAS Q61R -GTP switch (SW) regions and overall backbone are less flexible than observed in KRAS4b-GTP. The SW region rigidification was validated in heteronuclear NOE measurements. 31 P NMR experiments indicate that the G-domain of NRAS Q61R -GTP is in a predominant state 2 (active) conformation.","journal":"Biomolecular NMR Assignments","year":2025,"id":565207,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9376,"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":346055,"name":"Marco Tonelli","orcid":"0000-0002-7700-5745","position":1,"is_corresponding":false},{"id":795221,"name":"Marcin Dyba","orcid":"0000-0001-6311-6877","position":2,"is_corresponding":false},{"id":267816,"name":"William Gillette","orcid":"0000-0002-8592-3642","position":3,"is_corresponding":false},{"id":267809,"name":"Dominic Esposito","orcid":"0000-0002-9987-1687","position":4,"is_corresponding":false},{"id":233731,"name":"Dwight V. Nissley","orcid":"0000-0001-7523-116X","position":5,"is_corresponding":false},{"id":79462,"name":"Frank McCormick","orcid":"0000-0002-6619-7120","position":6,"is_corresponding":false},{"id":795223,"name":"Anna Maciąg","orcid":"0000-0001-6562-5640","position":7,"is_corresponding":false},{"id":795220,"name":"Alok K. Sharma","orcid":"0000-0001-8011-1074","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:56:28.709936Z","pmid":"40316884","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":[]}