{"doi":"10.1073/pnas.2413100121","title":"A molten globule ensemble primes Arf1–GDP for the nucleotide switch","abstract":"The adenosine di-phosphate (ADP) ribosylation factor (Arf) small guanosine tri-phosphate (GTP)ases function as molecular switches to activate signaling cascades that control membrane organization in eukaryotic cells. In Arf1, the GDP/GTP switch does not occur spontaneously but requires guanine nucleotide exchange factors (GEFs) and membranes. Exchange involves massive conformational changes, including disruption of the core β-sheet. The mechanisms by which this energetically costly switch occurs remain to be elucidated. To probe the switch mechanism, we coupled pressure perturbation with nuclear magnetic resonance (NMR), Fourier Transform infra-red spectroscopy (FTIR), small-angle X-ray scattering (SAXS), fluorescence, and computation. Pressure induced the formation of a classical molten globule (MG) ensemble. Pressure also favored the GDP to GTP transition, providing strong support for the notion that the MG ensemble plays a functional role in the nucleotide switch. We propose that the MG ensemble allows for switching without the requirement for complete unfolding and may be recognized by GEFs. An MG-based switching mechanism could constitute a pervasive feature in Arfs and Arf-like GTPases, and more generally, the evolutionarily related (Ras-like small GTPases) Rags and Gα GTPases.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":437248,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":318120,"name":"Noam Hantman","orcid":"0000-0002-5780-8356","position":1,"is_corresponding":false},{"id":1246688,"name":"Edgar V Peters","orcid":null,"position":2,"is_corresponding":false},{"id":1246086,"name":"Michel W. Jaworek","orcid":"0000-0002-5836-2464","position":3,"is_corresponding":false},{"id":720982,"name":"Jinqiu Wang","orcid":"0000-0001-5868-1935","position":4,"is_corresponding":false},{"id":1246689,"name":"S. B. Zhang","orcid":null,"position":5,"is_corresponding":false},{"id":426150,"name":"Scott A. McCallum","orcid":"0000-0002-6772-2150","position":6,"is_corresponding":false},{"id":367466,"name":"Richard E. Gillilan","orcid":"0000-0002-7636-3188","position":7,"is_corresponding":false},{"id":572214,"name":"Martin J. Fossat","orcid":"0000-0003-3078-2886","position":8,"is_corresponding":false},{"id":568727,"name":"Christian Roumestand","orcid":"0000-0002-4082-3293","position":9,"is_corresponding":false},{"id":808075,"name":"Amin Sagar","orcid":"0000-0002-6207-9557","position":10,"is_corresponding":false},{"id":1246087,"name":"Roland Winter","orcid":"0000-0002-3512-6928","position":11,"is_corresponding":false},{"id":257865,"name":"Pau Bernadó","orcid":"0000-0001-7395-5922","position":12,"is_corresponding":false},{"id":548781,"name":"Jacqueline Cherfils","orcid":"0000-0002-8966-3067","position":13,"is_corresponding":false},{"id":646036,"name":"Catherine A. Royer","orcid":"0000-0002-2670-3391","position":14,"is_corresponding":false},{"id":1246687,"name":"Tejaswi Koduru","orcid":null,"position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T02:00:29.872940Z","pmid":"39292747","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":[]}